{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:43:13Z","timestamp":1790959393517,"version":"4.1.0"},"reference-count":316,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Applied Molecular Bio-sciences Unit - UCIBIO","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Applied Molecular Bio-sciences Unit - UCIBIO","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Applied Molecular Bio-sciences Unit - UCIBIO","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"national funds from Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"national funds from Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"national funds from Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Therapeutic proteins, including monoclonal antibodies, single chain variable fragment (ScFv), crystallizable fragment (Fc), and fragment antigen binding (Fab), have accounted for one-third of all drugs on the world market. In particular, these medicines have been widely used in ocular therapies in the treatment of various diseases, such as age-related macular degeneration, corneal neovascularization, diabetic retinopathy, and retinal vein occlusion. However, the formulation of these biomacromolecules is challenging due to their high molecular weight, complex structure, instability, short half-life, enzymatic degradation, and immunogenicity, which leads to the failure of therapies. Various efforts have been made to overcome the ocular barriers, providing effective delivery of therapeutic proteins, such as altering the protein structure or including it in new delivery systems. These strategies are not only cost-effective and beneficial to patients but have also been shown to allow for fewer drug side effects. In this review, we discuss several factors that affect the design of formulations and the delivery of therapeutic proteins to ocular tissues, such as the use of injectable micro\/nanocarriers, hydrogels, implants, iontophoresis, cell-based therapy, and combination techniques. In addition, other approaches are briefly discussed, related to the structural modification of these proteins, improving their bioavailability in the posterior segments of the eye without affecting their stability. Future research should be conducted toward the development of more effective, stable, noninvasive, and cost-effective formulations for the ocular delivery of therapeutic proteins. In addition, more insights into preclinical to clinical translation are needed.<\/jats:p>","DOI":"10.3390\/pharmaceutics15010205","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T03:25:58Z","timestamp":1673234758000},"page":"205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Ocular Delivery of Therapeutic Proteins: A Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0968-0749","authenticated-orcid":false,"given":"Divyesh H.","family":"Shastri","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics & Pharmaceutical Technology, K.B. Institute of Pharmaceutical Education and Research, Kadi Sarva Vishwavidyalaya, Sarva Vidyalaya Kelavani Mandal, Gandhinagar 382016, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6923-0232","authenticated-orcid":false,"given":"Ana Catarina","family":"Silva","sequence":"additional","affiliation":[{"name":"FP-I3ID (Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento), FP-BHS (Biomedical and Health Sciences Research Unit), Faculty of Health Sciences, University Fernando Pessoa, 4249-004 Porto, Portugal"},{"name":"UCIBIO (Research Unit on Applied Molecular Biosciences), REQUIMTE (Rede de Qu\u00edmica e Tecnologia), MEDTECH (Medicines and Healthcare Products), Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0799-2335","authenticated-orcid":false,"given":"Hugo","family":"Almeida","sequence":"additional","affiliation":[{"name":"UCIBIO (Research Unit on Applied Molecular Biosciences), REQUIMTE (Rede de Qu\u00edmica e Tecnologia), MEDTECH (Medicines and Healthcare Products), Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Mesosystem Investiga\u00e7\u00e3o & Investimentos by Spinpark, Barco, 4805-017 Guimar\u00e3es, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1080\/17425247.2021.1846518","article-title":"Recent advances in intraocular and novel drug delivery systems for the treatment of diabetic retinopathy","volume":"18","author":"Sharma","year":"2021","journal-title":"Expert Opin. Drug Del."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kim, H.M., and Woo, S.J. (2021). Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010108"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e888","DOI":"10.1016\/S2214-109X(17)30293-0","article-title":"Vision Loss Expert Group. Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: A systematic review and meta-analysis","volume":"5","author":"Bourne","year":"2017","journal-title":"Lancet Glob. Health"},{"key":"ref_4","first-page":"6654168","article-title":"Intravitreal Therapy for Diabetic Macular Edema: An Update","volume":"2021","author":"Claudio","year":"2021","journal-title":"J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0039-6257(02)00391-0","article-title":"The potential role of PKC b in diabetic retinopathy and macular edema","volume":"47","author":"Aiello","year":"2002","journal-title":"Survey Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jsps.2018.08.001","article-title":"Preparation, characterization, and antibacterial activity of diclofenac-loaded chitosan nanoparticles","volume":"27","author":"Alqahtani","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3436415","DOI":"10.1155\/2016\/3436415","article-title":"Combination of Intrastromal and Intracameral Injections of Amphotericin B in the Treatment of Severe Fungal Keratitis","volume":"2016","author":"Hu","year":"2016","journal-title":"J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"113","DOI":"10.4103\/0975-8453.75042","article-title":"Ophthalmic drug delivery system: Challenges and approaches","volume":"1","author":"Patel","year":"2010","journal-title":"Syst. Rev. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1167\/tvst.8.1.12","article-title":"Characterization of Biodegradable Microsphere-Hydrogel Ocular Drug Delivery System for Controlled and Extended Release of Ranibizumab. Transl","volume":"8","author":"Liu","year":"2019","journal-title":"Vis. Sci. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s43094-021-00331-2","article-title":"Recent advances in ocular drug delivery systems and targeting VEGF receptors for management of ocular angiogenesis: A comprehensive review","volume":"7","author":"Narayana","year":"2021","journal-title":"Future J. Pharm. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.2147\/DDDT.S378450","article-title":"Brolucizumab for the Treatment of Degenerative Macular Conditions: A Review of Clinical Studies","volume":"16","author":"Karasavvidou","year":"2022","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1056\/NEJMoa054481","article-title":"Ranibizumab for neovascular age-related macular degeneration","volume":"355","author":"Rosenfeld","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1016\/j.ophtha.2007.09.012","article-title":"Pharmacokinetics of intravitreal ranibizumab (Lucentis)","volume":"114","author":"Bakri","year":"2007","journal-title":"Ophthalmology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.ajo.2012.03.047","article-title":"Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans","volume":"154","author":"Krohne","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1097\/IAE.0b013e318134eecd","article-title":"Pharmacokinetics, and retinal distribution of ranibizumab, a humanized antibody fragment directed against VEGF-A, following intravitreal administration in rabbits","volume":"27","author":"Gaudreault","year":"2007","journal-title":"Retina"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6501","DOI":"10.1167\/iovs.15-17279","article-title":"Ranibizumab and Aflibercept: Intraocular Pharmacokinetics and Their Effects on Aqueous VEGF Level in Vitrectomized and Nonvitrectomized Macaque Eyes","volume":"56","author":"Niwa","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1167\/iovs.16-19204","article-title":"Intraocular Pharmacokinetics of Intravitreal Aflibercept (Eylea) in a Rabbit Model","volume":"57","author":"Park","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.ophtha.2007.01.017","article-title":"Pharmacokinetics of intravitreal bevacizumab (Avastin)","volume":"114","author":"Bakri","year":"2007","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.ajo.2008.05.036","article-title":"Intraocular pharmacokinetics of bevacizumab after a single intravitreal injection in humans","volume":"146","author":"Krohne","year":"2008","journal-title":"Am. J. Ophthalmol."},{"key":"ref_20","first-page":"e53878","article-title":"Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs","volume":"113","author":"Ahn","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5899","DOI":"10.1167\/iovs.10-6862","article-title":"PET\/CT imaging of I-124-radiolabeled bevacizumab and ranibizumab after intravitreal injection in a rabbit model","volume":"5","author":"Christoforidis","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s13346-010-0009-8","article-title":"Intravitreal poly(L-lactide) microparticles sustain retinal and choroidal delivery of TG-0054, a hydrophilic drug intended for neovascular diseases","volume":"1","author":"Shelke","year":"2011","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"697","DOI":"10.2147\/OPTH.S19555","article-title":"Pharmacokinetics of intravitreal bevacizumab (Avastin(R)) in rabbits","volume":"5","author":"Sinapis","year":"2011","journal-title":"Clin. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.1167\/iovs.08-3148","article-title":"Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits","volume":"50","author":"Nomoto","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1097\/IAE.0b013e318217373c","article-title":"Intraocular pharmacokinetics after a single intravitreal injection of 1.5 mg versus 3.0 mg of bevacizumab in humans","volume":"31","author":"Meyer","year":"2011","journal-title":"Retina"},{"key":"ref_26","unstructured":"(2022, June 30). Center for Drug Evaluation and Research Application Number 761125Orig1s000. Clinical Pharmacology Reviews, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2019\/761125Orig1s000ClinPharmR.pdf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1080\/13543784.2020.1772754","article-title":"Abicipar pegol: An investigational anti-VEGF agent for the treatment of wet age-related macular degeneration","volume":"29","author":"Traverso","year":"2020","journal-title":"Expert Opin. Investig. Drugs."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/13543784.2021.1879791","article-title":"Faricimab: An investigational agent targeting the Tie-2\/angiopoietin pathway and VEGF-A for the treatment of retinal diseases","volume":"30","author":"Vagge","year":"2021","journal-title":"Expert Opin. Investig. Drugs."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0140-6736(22)00018-6","article-title":"Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): Two randomised, double-masked, phase 3 trials","volume":"399","author":"Wykoff","year":"2022","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"696201","DOI":"10.3389\/fphar.2021.696201","article-title":"Conbercept for Treatment of Neovascular Age-Related Macular Degeneration and Visual Impairment due to Diabetic Macular Edema or Pathologic Myopia Choroidal Neovascularization: A Systematic Review and Meta-Analysis","volume":"12","author":"Zhou","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.exer.2006.02.010","article-title":"Pegaptanib for the treatment of age-related macular degeneration","volume":"83","author":"Zhou","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.clinthera.2006.01.009","article-title":"Pegaptanib sodium for the treatment of neovascular age-related macular degeneration: A review","volume":"28","author":"Kourlas","year":"2006","journal-title":"Clin. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"653","DOI":"10.2147\/OPTH.S236637","article-title":"The Evolving Treatment of Diabetic Retinopathy","volume":"14","author":"Mansour","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1196\/annals.1348.062","article-title":"Anti-VEGF aptamer (pegaptanib) therapy for ocular vascular diseases","volume":"1082","author":"Ng","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.addr.2018.01.016","article-title":"Improving Long-Term Subcutaneous Drug Delivery by Regulating Material-Bioenvironment Interaction","volume":"127","author":"Chen","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ijpharm.2013.02.030","article-title":"Approaches for Enhancing Oral Bioavailability of Peptides and Proteins","volume":"447","author":"Renukuntla","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"953","DOI":"10.2165\/00003495-199345060-00007","article-title":"Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders","volume":"45","author":"Faulds","year":"1993","journal-title":"Drugs"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1517\/17425247.2.1.29","article-title":"Commercial Challenges of Protein Drug Delivery","volume":"2","author":"Brown","year":"2005","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.jconrel.2020.09.005","article-title":"Release of functional dexamethasone by intracellular enzymes: A modular peptide-based strategy for ocular drug delivery","volume":"327","author":"Bhattacharya","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"114097","DOI":"10.1016\/j.addr.2021.114097","article-title":"Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers","volume":"182","author":"Haddadzadegan","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"661","DOI":"10.2174\/138920009789895499","article-title":"Pharmacokinetics of Biotech Drugs: Peptides, Proteins and Monoclonal Antibodies","volume":"10","author":"Lin","year":"2009","journal-title":"Curr. Drug Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0378-5173(87)90092-5","article-title":"Disposition of Timolol and Inulin in the Rabbit Eye Following Corneal versus Non-Corneal Absorption","volume":"38","author":"Ahmed","year":"1987","journal-title":"Int. J. Pharm."},{"key":"ref_43","first-page":"863","article-title":"Absorption of Polyethylene Glycols 600 Through 2000: The Molecular Weight Dependence of Gastrointestinal and Nasal Absorption","volume":"7","author":"Donovan","year":"1990","journal-title":"Pharm. Res. Off. J. Am. Assoc. Pharm. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1111\/ijfs.14048","article-title":"Intestinal Absorption of Small Peptides: A Review","volume":"54","author":"Shen","year":"2019","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jconrel.2013.01.018","article-title":"Nanoparticle Diffusion in, and Microrheology of, the Bovine Vitreous Ex Vivo","volume":"167","author":"Xu","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1023\/A:1007517912927","article-title":"Permeability and Diffusion in Vitreous Humor: Implications for Drug Delivery","volume":"17","author":"Xu","year":"2000","journal-title":"Pharm. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s11095-010-0356-7","article-title":"Contribution of Saccadic Motion to Intravitreal Drug Transport: Theoretical Analysis","volume":"28","author":"Balachandran","year":"2011","journal-title":"Pharm. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1016\/j.bpj.2015.10.002","article-title":"Diffusion Regulation in the Vitreous Humor","volume":"109","author":"Arends","year":"2015","journal-title":"Biophys. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3109\/03602532.2014.921190","article-title":"Ocular Cytochrome P450s and Transporters: Roles in Disease and Endobiotic and Xenobiotic Disposition","volume":"46","author":"Nakano","year":"2014","journal-title":"Drug Metab. Biophys. J. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Urtti, A. (2012). Nanostructures Overcoming the Ocular Barrier: Drug Delivery Strategies, Royal Society of Chemistry. Chapter 4.2.","DOI":"10.1039\/9781849735292-00190"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1172\/JCI120429","article-title":"Gene therapy and genome surgery in the retina","volume":"128","author":"DiCarlo","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/aos.14249","article-title":"Subretinal Surgery: Functional and Histological Consequences of Entry into the Subretinal Space","volume":"97","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1016\/j.drudis.2019.02.001","article-title":"Design Principles of Ocular Drug Delivery Systems: Importance of Drug Payload, Release Rate, and Material Properties","volume":"24","author":"Subrizi","year":"2019","journal-title":"Drug Discov. Today."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Bachu, R.D., Chowdhury, P., Al-Saedi, Z.H.F., Karla, P.K., and Boddu, S.H.S. (2018). Ocular Drug Delivery Barriers-Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10010028"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.jsps.2014.06.004","article-title":"A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives","volume":"24","author":"Muheem","year":"2016","journal-title":"Saudi Pharm. J."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Leclercq, B., Mejlachowicz, D., and Behar-Cohen, F. (2022). Ocular Barriers and Their Influence on Gene Therapy Products Delivery. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14050998"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2174\/138920007779815968","article-title":"Diffusion of macromolecule through retina after experimental branch retinal vein occlusion and estimate of intraretinal barrier","volume":"8","author":"Tao","year":"2007","journal-title":"Curr. Drug Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1167\/iovs.02-1027","article-title":"Human retinal molecular weight exclusion limit and estimate of species variation","volume":"44","author":"Jackson","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","first-page":"1525","article-title":"Hyaluronic Acid-PEG-Based Diels\u2013Alder In Situ Forming Hydrogels for Sustained Intraocular Delivery of Bevacizumab","volume":"23","author":"Blessing","year":"2022","journal-title":"Biomacromolecules"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s13346-018-0520-x","article-title":"Freeze-dried matrices for ocular administration of bevacizumab: A comparison between subconjunctival and intravitreal administration in rabbits","volume":"8","author":"Burgalassi","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.addr.2006.07.027","article-title":"Challenges and obstacles of ocular pharmacokinetics and drug delivery","volume":"58","author":"Urtti","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.idc.2009.06.008","article-title":"Pharmacokinetics and pharmacodynamics of antibacterial agents","volume":"23","author":"Levison","year":"2009","journal-title":"Infect. Dis. Clini. N. Am."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.exer.2015.05.003","article-title":"Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data","volume":"137","author":"Urtti","year":"2015","journal-title":"Exp. Eye. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/scitranslmed.aac4882","article-title":"The peptidomimetic Vasotide targets two retinal VEGF receptors and reduces pathological angiogenesis in murine and nonhuman primate models of retinal disease","volume":"7","author":"Sidman","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1111\/j.2042-7158.2010.01153.x","article-title":"In-vitro permeation of bevacizumab through human sclera: Effect of iontophoresis application","volume":"62","author":"Pescina","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s13318-013-0126-0","article-title":"Impact of physiochemical properties on pharmacokinetics of protein therapeutics","volume":"38","author":"Swami","year":"2013","journal-title":"Eur. J. Drug Metab. Pharmacokinetics."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s10875-010-9468-4","article-title":"Neonatal Fc receptor: From immunity to therapeutics","volume":"30","author":"Kuo","year":"2010","journal-title":"J. Clin. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1208\/s12248-010-9183-3","article-title":"Ocular Drug Delivery","volume":"12","author":"Gaudana","year":"2010","journal-title":"AAPS J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5403","DOI":"10.1167\/iovs.10-5392","article-title":"Ophthalmic drug delivery systems for the treatment of retinal diseases: Basic research to clinical applications","volume":"51","author":"Edelhauser","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1167\/iovs.13-13650","article-title":"Ocular pharmacokinetics of intravitreally administered brimonidine and dexamethasone in animal models with and without blood-retinal barrier breakdown","volume":"55","author":"Shen","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jconrel.2014.06.043","article-title":"Ocular delivery of macromolecules","volume":"190","author":"Kim","year":"2014","journal-title":"J. Con. Rel."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"683","DOI":"10.2217\/nnm-2016-0379","article-title":"Drug delivery to the eye: What benefits do nanocarriers offer?","volume":"12","author":"Joseph","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1517\/17425247.1.1.99","article-title":"Periocular routes for retinal drug delivery","volume":"1","author":"Raghava","year":"2004","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"975032","DOI":"10.1155\/2013\/975032","article-title":"Retinal pigment epithelial cells express a functional receptor for glucagon-like peptide-1 (GLP-1)","volume":"2013","author":"Puddu","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/nchem.2629","article-title":"Materials and methods for delivery of biological drugs","volume":"8","author":"Zelikin","year":"2016","journal-title":"Nat. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.survophthal.2012.01.007","article-title":"Corneal neovascularization: An anti-VEGF therapy review","volume":"57","author":"Chang","year":"2012","journal-title":"Surv. Ophthalmol."},{"key":"ref_77","first-page":"263","article-title":"Pegaptanib in the treatment of wet, age-related macular degeneration","volume":"1","author":"Vinores","year":"2006","journal-title":"Int. J. Nanomed."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1080\/17425247.2016.1227783","article-title":"Recent perspectives on the delivery of biologics to back of the eye","volume":"14","author":"Joseph","year":"2016","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1167\/iovs.12-10260","article-title":"Pharmacokinetics of ranibizumab in patients with neovascular age-related macular degeneration: A population approach","volume":"54","author":"Xu","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/wnan.1272","article-title":"Controlled ocular drug delivery with nanomicelles, Wiley interdisciplinary reviews","volume":"6","author":"Vaishya","year":"2014","journal-title":"Nanomed. Nanobiotechnol."},{"key":"ref_81","first-page":"331","article-title":"Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes. Graefe\u2019s Arch","volume":"252","author":"Moisseiev","year":"2014","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_82","first-page":"1","article-title":"Aflibercept\u2014How does it compare with other Anti-VEGF Drugs?","volume":"1","author":"Sharma","year":"2014","journal-title":"Aust. J. Clin. Ophthalmol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"290","DOI":"10.4103\/0974-9233.71588","article-title":"Giovannini, Adalimumab (humira) in ophthalmology: A review of the literature","volume":"17","author":"Neri","year":"2010","journal-title":"Middle East Afr. J. Ophthalmol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.preteyeres.2008.11.005","article-title":"Therapeutic monoclonal antibodies in ophthalmology","volume":"28","author":"Rodrigues","year":"2009","journal-title":"Prog. Ret. Eye Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"613","DOI":"10.4161\/mabs.2.6.13333","article-title":"Charge variants in IgG1: Isolation, characterization, In vitro binding properties and pharma-cokinetics in rats","volume":"2","author":"Khawli","year":"2010","journal-title":"MAbs"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0014-4835(65)80052-5","article-title":"The distribution and movement of serum albumin in the cornea","volume":"4","author":"Maurice","year":"1965","journal-title":"Exp. Eye Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0014-4835(71)90143-6","article-title":"Solute permeability of the corneal endothelium and Descemet\u2019s membrane","volume":"12","author":"Kim","year":"1971","journal-title":"Exp. Eye Res."},{"key":"ref_88","first-page":"1893","article-title":"Human scleral permeability. Effects of age, cryotherapy, transscleral diode laser, and surgical thinning","volume":"36","author":"Olsen","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrd4363","article-title":"Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies","volume":"13","author":"Mitragotri","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1517\/14712598.3.1.45","article-title":"Drug delivery to the retina: Challenges and opportunities","volume":"3","author":"Duvvuri","year":"2003","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/s11095-009-0045-6","article-title":"Stability of protein pharmaceuticals: An update","volume":"27","author":"Manning","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.jpba.2010.12.027","article-title":"Effective electrophoretic mobilities and charges of anti-VEGF proteins determined by capillary zone electrophoresis","volume":"55","author":"Li","year":"2011","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3233\/HAB-2011-0244","article-title":"Effects of dilution and prolonged storage with preservative in a polyethylene container on Bevacizumab (Avastin) for topical delivery as a nasal spray in anti-hereditary hemorrhagic telangiectasia and related therapies","volume":"20","author":"Kaja","year":"2011","journal-title":"Hum. Antibodies"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1021\/acs.biomac.7b00587","article-title":"Controlled antibody release from degradable thermoresponsive hydrogels cross-linked by Diels-Alder chemistry","volume":"18","author":"Gregoritza","year":"2017","journal-title":"Biomacromolecules"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Jani, R., Lang, J., Rodeheaver, D., Missel, P., Roehrs, R., and Chowhan, M. (2002). Design and Evaluation of Ophthalmic Pharmaceutical Products, Modern Pharmaceutics, CRC Press. [4th ed.].","DOI":"10.1201\/9780824744694.ch13"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.addr.2006.07.022","article-title":"Industrial perspective in ocular drug delivery","volume":"58","author":"Ali","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11095-014-1456-6","article-title":"Oxidative stress protection by exogenous delivery of rhHsp70 chaperone to the retinal pigment epithelium (RPE), a possible therapeutic strategy against RPE degeneration","volume":"32","author":"Subrizi","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nchembio.2006","article-title":"Protein aggregation: A rescue by chaperones","volume":"12","author":"Schymkowitz","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"148039","DOI":"10.1155\/2012\/148039","article-title":"Proteomic Analyses of the Vitreous Humour","volume":"2012","author":"Angi","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1559-0275-11-29","article-title":"Proteomic Analysis of Human Vitreous Humor","volume":"11","author":"Murthy","year":"2014","journal-title":"Clin. Proteom."},{"key":"ref_101","first-page":"31","article-title":"N-Acetylcarnosine Sustained Drug Delivery Eye Drops to Control the Signs of Ageless Vision: Glare Sensitivity, Cataract Amelioration and Quality of Vision Currently Available Treatment for the Challenging 50,000-Patient Population","volume":"4","author":"Babizhayev","year":"2009","journal-title":"Clin. Interv. Aging"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1080\/02713683.2019.1565890","article-title":"Morphology and Composition of the Inner Limiting Membrane: Species-Specific Variations and Relevance toward Drug Delivery Research","volume":"44","author":"Peynshaert","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1128\/JVI.00200-16","article-title":"Impact of Heparan Sulfate Binding on Transduction of Retina by Recombinant Adeno-Associated Virus Vectors","volume":"90","author":"Boye","year":"2016","journal-title":"J. Virol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jpha.2017.06.008","article-title":"Development of a Novel Stability Indicating RP-HPLC Method for Quantification of Connexin43 Mimetic Peptide and Determination of Its Degradation Kinetics in Biological Fluids","volume":"7","author":"Bisht","year":"2017","journal-title":"J. Pharm. Anal."},{"key":"ref_105","first-page":"87","article-title":"Polymorphic metabolism of flestolol and other ester containing compounds by a carboxylesterase in New Zealand white rabbit blood and cornea","volume":"88","author":"Stampfli","year":"1995","journal-title":"Res. Commun. Mol. Pathol. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","article-title":"Peptide Therapeutics: Current Status and Future Directions","volume":"20","author":"Fosgerau","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nri3459","article-title":"Immunology of age-related macular degeneration","volume":"13","author":"Ambati","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.drudis.2016.10.015","article-title":"Protein delivery to the back of the eye: Barriers, carriers and stability of anti-VEGF proteins","volume":"22","author":"Radhakrishnan","year":"2017","journal-title":"Drug Discov. Today."},{"key":"ref_109","first-page":"3299","article-title":"Elevated levels of proteolytic enzymes in the aging human vitreous","volume":"41","author":"Gilbert","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"20557","DOI":"10.3390\/molecules191220557","article-title":"Role of Protease-Inhibitors in Ocular Diseases","volume":"19","author":"Pescosolido","year":"2014","journal-title":"Molecules"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1089\/jop.2010.0188","article-title":"Ocular Sustained Release Nanoparticles Containing Stereoiso-meric Dipeptide Prodrugs of Acyclovir","volume":"27","author":"Jwala","year":"2011","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/(SICI)1097-0215(19991029)83:3<326::AID-IJC7>3.0.CO;2-X","article-title":"Terminal Modifications Inhibit Proteolytic Degradation of an Immunogenic MART-127-35 Peptide: Implications for Peptide Vaccines","volume":"83","author":"Brinckerhoff","year":"1999","journal-title":"Int. J. Cancer"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00726-005-0289-3","article-title":"Strategies to Improve Plasma Half Life Time of Peptide and Protein Drugs","volume":"30","author":"Werle","year":"2006","journal-title":"Amino Acids"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1517\/17425247.2.5.891","article-title":"Ophthalmic Drug Delivery Considerations at the Cellular Level: Drug-Metabolising Enzymes and Transporters","volume":"2","author":"Attar","year":"2005","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"623","DOI":"10.3109\/02713688709025223","article-title":"Cytochrome P450, Drug Metabolizing Enzymes and Arachidonic Acid Metabolism in Bovine Ocular Tissues","volume":"6","author":"Schwartzman","year":"1987","journal-title":"Curr. Eye Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0039-6257(83)90125-X","article-title":"Lysosomal Enzymes in Ocular Tissues and Diseases","volume":"27","author":"Hayasaka","year":"1983","journal-title":"Surv. Ophthalmol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2217\/17435889.2.1.11","article-title":"Ocular Drug Delivery: Nanomedicine Applications","volume":"2","author":"Vandervoort","year":"2007","journal-title":"Nanomedicine"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nrd.2015.17","article-title":"Ten years of anti-vascular endothelial growth factor therapy","volume":"15","author":"Ferrara","year":"2016","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_119","first-page":"6","article-title":"Aflibercept approved for macular degeneration","volume":"69","author":"Traynor","year":"2012","journal-title":"Am. J. Health Sys. Pharm."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nrd1955","article-title":"Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease","volume":"5","author":"Ng","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1097\/MAJ.0b013e3180318fbc","article-title":"Tumor necrosis factor antagonists: Preliminary evidence for an emerging approach in the treatment of ocular inflammation","volume":"27","author":"Theodossiadis","year":"2007","journal-title":"Retina"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1001\/archopht.116.9.1218","article-title":"Efficacy of hyaluronidase in reducing increases in intraocular pressure related to the use of viscoelastic substances","volume":"116","author":"Harooni","year":"1998","journal-title":"Arch. Ophthalmol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1021\/cr050247k","article-title":"Hyaluronidases: Their genomics, structures, and mechanisms of action","volume":"106","author":"Stern","year":"2006","journal-title":"Chem. Rev."},{"key":"ref_124","first-page":"3075","article-title":"Widespread expression of an exogenous gene in the eye after intravenous administration","volume":"43","author":"Zhu","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_125","first-page":"100642","article-title":"CD44 Aptamer Mediated Cargo Delivery to Lysosomes of Retinal Pigment Epithelial Cells to Prevent Age-Related Macular Degeneration","volume":"18","author":"Chandola","year":"2019","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"5142","DOI":"10.1039\/C9TB01043B","article-title":"Fmoc-Diphenylalanine as a Suitable Building Block for the Preparation of Hybrid Materials and Their Potential Applications","volume":"7","author":"Diaferia","year":"2019","journal-title":"J. Mater. Chem. B"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1159\/000513048","article-title":"Brolucizumab: A Newly Developed Anti-VEGF Molecule for the Treatment of Neovascular Age-Related Macular Degeneration","volume":"244","author":"Tadayoni","year":"2021","journal-title":"Ophthalmologica"},{"key":"ref_128","first-page":"671","article-title":"An explanation for the long duration of mydriatic effect of atropine in eye","volume":"15","author":"Salazar","year":"1976","journal-title":"Investig. Ophthalmol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.addr.2017.12.008","article-title":"Implications of Melanin Binding in Ocular Drug Delivery","volume":"126","author":"Reinisalo","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_130","first-page":"384","article-title":"The Ocular Deposition of Chloroquine","volume":"2","author":"Bernstein","year":"1963","journal-title":"Investig. Ophthalmol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1167\/iovs.12-10169","article-title":"Assessing a Novel Depot Delivery Strategy for Noninvasive Administration of VEGF\/PDGF RTK Inhibitors for Ocular Neovascular Disease","volume":"54","author":"Robbie","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ophtha.2019.07.011","article-title":"Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial","volume":"127","author":"Liao","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1167\/tvst.7.4.21","article-title":"A Controlled Release System for Long-Acting Intravitreal Delivery of Small Molecules","volume":"7","author":"Machinaga","year":"2018","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"120924","DOI":"10.1016\/j.ijpharm.2021.120924","article-title":"Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies","volume":"607","author":"Mofidfar","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"4167","DOI":"10.1002\/jps.21278","article-title":"The Pharmacology of PEGylation: Balancing PD with PK to Generate Novel Therapeutics","volume":"97","author":"Fishburn","year":"2008","journal-title":"J. Pharm. Sci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1076\/ceyr.26.3.151.14893","article-title":"Novel dipeptide prodrugs of acyclovir for ocular herpes infections: Bioreversion, antiviral activity and transport across rabbit cornea","volume":"26","author":"Anand","year":"2003","journal-title":"Curr. Eye. Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1515\/biol-2018-0035","article-title":"Nanoparticles as Carriers of Proteins, Peptides and Other Therapeutic Molecules","volume":"13","author":"Pudlarz","year":"2018","journal-title":"Open Life Sci."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0169-409X(95)00018-3","article-title":"Delivery systems for intraocular routes","volume":"16","author":"Peyman","year":"1995","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1517\/17425247.4.4.371","article-title":"Novel approaches to retinal drug delivery","volume":"4","author":"Janoria","year":"2007","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_140","first-page":"1","article-title":"Current ocular drug delivery challenges","volume":"33","author":"Lambert","year":"2005","journal-title":"Drug Dev. Rep. Ind. Overv. Details"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0169-409X(95)00012-V","article-title":"Recent developments in ophthalmic drug delivery: Conventional ocular formulations","volume":"16","author":"Lang","year":"1995","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1167\/iovs.06-0670","article-title":"Assessment of subconjunctival and intrascleral drug delivery to the posterior segment using dynamic contrast-enhanced magnetic resonance imaging","volume":"48","author":"Kim","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2147\/IJN.S184574","article-title":"Neuroprotective effect of insulin-loaded chitosan nanoparticles\/PLGA-PEG-PLGA hydrogel on diabetic retinopathy in rats","volume":"14","author":"Rong","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1021\/cr200157d","article-title":"Hydrogels for protein delivery","volume":"112","author":"Vermonden","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ejpb.2015.05.016","article-title":"Hydrogels in ophthalmic applications","volume":"95","author":"Kirchhof","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1167\/tvst.4.2.5","article-title":"Injectable chemically crosslinked hydrogel for the controlled release of bevacizumab in vitreous: A 6-month in vivo study","volume":"4","author":"Yu","year":"2015","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ejpb.2019.04.006","article-title":"Ultrafast in situ forming poly(ethylene glycol)-poly(amido amine) hydrogels with tunable drug release properties via controllable degradation rates","volume":"139","author":"Buwalda","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1021\/acs.biomac.6b01604","article-title":"Hydrogels for therapeutic delivery: Current developments and future directions","volume":"18","author":"Buwalda","year":"2017","journal-title":"Biomacromolecules"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"5371","DOI":"10.1039\/c3tb20940g","article-title":"Injectable biodegradable hydrogels: Progress and challenges","volume":"1","author":"Bae","year":"2013","journal-title":"J. Mater. Chem. B"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0168-3659(99)00074-7","article-title":"Degradable dextran hydrogels: Controlled release of a model protein from cylinders and microspheres","volume":"60","author":"Franssen","year":"1999","journal-title":"J. Control. Release."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.addr.2006.09.004","article-title":"Hydrogels in controlled release formulations: Network design and mathematical modeling","volume":"58","author":"Lin","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.jconrel.2009.06.003","article-title":"Photopolymerized thermosensitive hydrogels for tailorable diffusion-controlled protein delivery","volume":"140","author":"Censi","year":"2009","journal-title":"J. Control. Release."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"3358","DOI":"10.1021\/acs.molpharmaceut.5b00375","article-title":"Diels-alder hydrogels for controlled antibody release: Correlation between mesh size and release rate","volume":"12","author":"Kirchhof","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"116","DOI":"10.4103\/0975-1483.63144","article-title":"Studies on in situ hydrogel: A smart way for safe and sustained ocular drug delivery","volume":"2","author":"Shastri","year":"2010","journal-title":"J. Young Pharm."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1002\/jbm.a.31811","article-title":"Effects of sterilization on poly(ethylene glycol) hydrogels","volume":"87","author":"Kanjickal","year":"2008","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"600","DOI":"10.3109\/10837450.2015.1035728","article-title":"Preparation and in vitro\/in vivo evaluation of antimicrobial ocular in situ gels containing a disappearing preservative for topical treatment of bacterial conjunctivitis","volume":"21","author":"Saher","year":"2016","journal-title":"Pharm. Dev. Technol."},{"key":"ref_157","first-page":"222","article-title":"In-vitro release of Bevacizumab from hydrogel-based drug delivery systems","volume":"56","author":"Janet","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jconrel.2020.07.031","article-title":"Intravitreal hydrogels for sustained release of therapeutic proteins","volume":"326","author":"Blessing","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_159","first-page":"1941","article-title":"Controlled release bevacizumab in thermoresponsive hydrogel found to inhibit angiogenesis","volume":"24","author":"Hu","year":"2014","journal-title":"Biomed. Mater. Eng."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1021\/bm2009558","article-title":"Extended release of bevacizumab by thermosensitive biodegradable and biocompatible hydrogel","volume":"13","author":"Wang","year":"2012","journal-title":"Biomacromolecules"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ejpb.2014.12.029","article-title":"Silk hydrogels for sustained ocular delivery of anti-vascular endothelial growth factor (anti- VEGF) therapeutics","volume":"95","author":"Lovett","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1021\/mp300716t","article-title":"Light activated, in situ forming gel for sustained suprachoroidal delivery of bevacizumab","volume":"10","author":"Tyagi","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"6541","DOI":"10.1016\/j.biomaterials.2009.08.025","article-title":"Subconjunctivally implantable hydrogels with degradable and thermoresponsive properties for sustained release of insulin to the retina","volume":"30","author":"Misra","year":"2009","journal-title":"Biomaterials"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1089\/jop.2009.0059","article-title":"Sustained subconjunctival protein delivery using a thermosetting gel delivery system","volume":"26","author":"Rieke","year":"2010","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.addr.2022.114342","article-title":"Polymer based sustained drug delivery to the ocular posterior segment: Barriers and future opportunities for the treatment of neovascular pathologies","volume":"187","author":"Alshaikh","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1167\/iovs.13-13120","article-title":"Biocompatible reverse thermal gel sustains the release of intravitreal bevacizumab in vivo","volume":"55","author":"Rauck","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.biomaterials.2010.09.044","article-title":"A functionalizable reverse thermal gel based on a polyurethane\/PEG block copolymer","volume":"32","author":"Park","year":"2011","journal-title":"Biomaterials"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.actbio.2016.05.011","article-title":"Thermosensitive hexanoyl glycol chitosan-based ocular delivery system for glaucoma therapy","volume":"39","author":"Cho","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_169","first-page":"4629","article-title":"Pentablock Copolymer nano formulation for controlled Ocular Delivery of Protein Therapeutics","volume":"55","author":"Joseph","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.ejpb.2014.07.005","article-title":"Polyethylene glycol (PEG)-Poly(N- isopropylacrylamide) (PNIPAAm) based thermosensitive injectable hydrogels for biomedical applications","volume":"88","author":"Alexander","year":"2014","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Cano, J.J., Sigen, A., Andr\u00e9s-Guerrero, V., Tai, H., Bravo-Osuna, I., Molina-Mart\u00ednez, I.T., Wang, W., and Herrero-Vanrell, R. (2021). Thermo-Responsive PLGA-PEG-PLGA Hydrogels as Novel Injectable Platforms for Neuroprotective Combined Therapies in the Treatment of Retinal Degenerative Diseases. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13020234"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1023\/A:1015841715384","article-title":"Controlled delivery systems for proteins based on poly(lactic\/glycolic acid) microspheres","volume":"8","author":"Cohen","year":"1991","journal-title":"Pharm. Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"4176","DOI":"10.1073\/pnas.90.9.4176","article-title":"Controlled release of polypeptides from polyanhydrides","volume":"90","author":"Ron","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/nrd1576","article-title":"Cyclodextrin-based pharmaceutics: Past, present and future","volume":"3","author":"Davis","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1073\/pnas.0600997103","article-title":"Role of target geometry in phagocytosis","volume":"103","author":"Champion","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1023\/B:PHAM.0000019305.79599.a5","article-title":"Poly(lactide-co-glycolide) microsphere formulations of darbepoetin alfa: Spray drying is an alternative to encapsulation by spray-freeze drying","volume":"21","author":"Burke","year":"2004","journal-title":"Pharm. Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.ijpharm.2015.04.075","article-title":"Reversible hydrophobic ion-paring complex strategy to minimize acylation of octreotide during long-term delivery from PLGA microparticles","volume":"489","author":"Vaishya","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1167\/iovs.01-1156","article-title":"Controlled delivery of the anti-VEGF aptamer EYE001 with poly(lactic-co-glycolic)acid microspheres","volume":"44","author":"Carrasquillo","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_179","first-page":"5123","article-title":"Preparation and Characterization of Pegaptanib Sustained Release Microsphere Formulations for Intraocular Application","volume":"47","author":"Cook","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.3109\/02713683.2015.1101140","article-title":"Controlled and Extended In vitro Release of Bioactive Anti-Vascular Endothelial Growth Factors from a Microsphere-Hydrogel Drug Delivery System","volume":"41","author":"Osswald","year":"2016","journal-title":"Curr. Eye Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.ijpharm.2015.11.002","article-title":"Extended release microparticle-in-gel formulation of octreotide: Effect of polymer type on acylation of peptide during In vitro release","volume":"496","author":"Vaishya","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Mahlumba, P., Choonara, Y.E., Kumar, P., du Toit, L.C., and Pillay, V. (2016). Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery. Molecules, 21.","DOI":"10.3390\/molecules21081002"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/s41433-020-0770-y","article-title":"Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases","volume":"34","author":"Seah","year":"2020","journal-title":"Eye"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3109\/02652040903052010","article-title":"Preparation and characteristics of interferon-alpha poly(lactic-co-glycolic acid) microspheres","volume":"27","author":"Yang","year":"2010","journal-title":"J. Microencap."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1089\/jop.2010.0158","article-title":"Comparison of long-acting bevacizumab formulations in the treatment of choroidal neovascularization in a rat model","volume":"27","author":"Pan","year":"2011","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Ramos, T.I., Villacis-Aguirre, C.A., Vispo, N.S., Padilla, L.S., Santana, S.P., Parra, N.C., and Alonso, J.R.T. (2021). Forms and Methods for Interferon\u2019s Encapsulation. Pharmaceutics, 13.","DOI":"10.20944\/preprints202108.0447.v1"},{"key":"ref_187","first-page":"118767","article-title":"Intravitreal anti-VEGF drug delivery systems for age-related macular degeneration","volume":"573","author":"Mondelo","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbagen.2004.11.009","article-title":"Depolymerized products of chitosan as potent inhibitors of tumor-induced angiogenesis","volume":"1722","author":"Tharanathan","year":"2005","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"36905","DOI":"10.1038\/srep36905","article-title":"An anti-TNF-alpha antibody mimetic to treat ocular inflammation","volume":"6","author":"Khalili","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Zamboulis, A., Nanaki, S., Michailidou, G., Koumentakou, I., Lazaridou, M., Ainali, N.M., Xanthopoulou, E., and Bikiaris, D.N. (2020). Chitosan and its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments. Polymers, 12.","DOI":"10.3390\/polym12071519"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/nbt.1601","article-title":"Enhanced antibody half-life improves in vivo activity","volume":"28","author":"Zalevsky","year":"2010","journal-title":"Nat. Biotech."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/S0022-2836(02)01443-2","article-title":"Effect of dextran on protein stability and conformation attributed to macromolecular crowding","volume":"326","author":"Sasahara","year":"2003","journal-title":"J. Mol. Biol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.addr.2015.02.005","article-title":"The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy","volume":"91","author":"Sockolosky","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.csbj.2019.09.004","article-title":"Recent Advancements in Non-Invasive Formulations for Protein Drug Delivery","volume":"17","author":"Bajracharya","year":"2019","journal-title":"Comp. Struct. Biotech. J."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"14189","DOI":"10.1073\/pnas.1616639113","article-title":"Supramolecular PEGylation of biopharmaceuticals","volume":"113","author":"Webber","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s11095-008-9745-6","article-title":"Investigating the movement of intravitreal human serum albumin nanoparticles in the vitreous and retina","volume":"26","author":"Kim","year":"2009","journal-title":"Pharm. Res."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s10384-009-0655-x","article-title":"Subretinal delivery of immunoglobulin G with gold nanoparticles in the rabbit eye","volume":"53","author":"Hayashi","year":"2009","journal-title":"Jap. J. Ophthalmol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nrd3745","article-title":"Ophthalmic drug discovery: Novel targets and mechanisms for retinal diseases and glaucoma","volume":"11","author":"Zhang","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_199","first-page":"6","article-title":"Protein Encapsulation into PLGA Nanoparticles by a Novel Phase Separation Method Using Non-Toxic Solvents","volume":"5","author":"Swed","year":"2014","journal-title":"J. Nanomed. Nanotechnol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2147\/IJN.S6428","article-title":"Pharmacokinetics, and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits","volume":"4","author":"Zhang","year":"2009","journal-title":"Int. J. Nanomed."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3109\/10611861003639796","article-title":"Brain-targeted delivery of tempol-loaded nanoparticles for neurological disorders","volume":"18","author":"Carroll","year":"2010","journal-title":"J. Drug Target."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.3390\/polym3031377","article-title":"Poly lactic-co-glycolic acid (plga) as biodegradable controlled drug delivery carrier","volume":"3","author":"Makadia","year":"2011","journal-title":"Polymers."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"De Negri Atanasio, G., Ferrari, P.F., Campardelli, R., Perego, P., and Palombo, D. (2020). Poly (Lactic-co-Glycolic Acid) Nanoparticles and Nanoliposomes for Protein Delivery in Targeted Therapy: A Comparative In Vitro Study. Polymers, 12.","DOI":"10.3390\/polym12112566"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.cep.2011.06.008","article-title":"Optimization of protein encapsulation in PLGA nanoparticles","volume":"50","author":"Feczko","year":"2011","journal-title":"Chem. Eng. Process."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.exer.2006.04.014","article-title":"A PEDF N- terminal peptide protects the retina from ischemic injury when delivered in PLGA nanospheres","volume":"83","author":"Li","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/j.biopha.2018.08.138","article-title":"A review on recent drug delivery systems for posterior segment of eye","volume":"107","author":"Nayak","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"6230","DOI":"10.1167\/iovs.10-6229","article-title":"Anti- inflammatory and antiangiogenic effects of nanoparticle-mediated delivery of a natural angiogenic inhibitor","volume":"52","author":"Jin","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/0092-8674(94)90200-3","article-title":"Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma","volume":"79","author":"Holmgren","year":"1994","journal-title":"Cell"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1161\/ATVBAHA.114.304627","article-title":"Nanoparticle-mediated expression of a Wnt pathway inhibitor ameliorates ocular neovascularization","volume":"35","author":"Wang","year":"2015","journal-title":"Arterioscler. Thromb. Vas. Bio."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1161\/ATVBAHA.115.305395","article-title":"Wnting out ocular neovascularization: Using nanoparticle delivery of very-low density lipoprotein receptor extracellular domain as Wnt pathway inhibitor in the retina","volume":"35","author":"Busik","year":"2015","journal-title":"Arterioscler. Thromb. Vas. Bio."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1021\/acs.molpharmaceut.5b00828","article-title":"Composite Nano-formulation Therapeutics for Long-Term Ocular Delivery of Macromolecules","volume":"13","author":"Agrahari","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"e1473","DOI":"10.1002\/wnan.1473","article-title":"Nanocarrier mediated retinal drug delivery: Overcoming ocular barriers to treat posterior eye diseases","volume":"10","author":"Bisht","year":"2017","journal-title":"WIREs Nanomed. Nanobiotechnol."},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Kelly, S.J., Hirani, A., Shahidadpury, V., Solanki, A., Halasz, K., Varghese Gupta, S., Madow, B., and Sutariya, V. (2018). Aflibercept Nanoformulation Inhibits VEGF Expression in Ocular In vitro Model: A Preliminary Report. Biomedicines, 6.","DOI":"10.3390\/biomedicines6030092"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"4676","DOI":"10.1021\/mp400487f","article-title":"Nanoparticles in porous microparticles prepared by supercritical infusion and pressure quench technology for sustained delivery of bevacizumab","volume":"10","author":"Yandrapu","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1021\/acs.molpharmaceut.6b00335","article-title":"PLGA microparticles entrapping chitosan-based nanoparticles for the ocular delivery of ranibizumab","volume":"13","author":"Elsaid","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1016\/j.actbio.2012.07.016","article-title":"Flt1 peptide-hyaluronate conjugate micelle-like nanoparticles encapsulating genistein for the treatment of ocular neovascularization","volume":"8","author":"Kim","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1016\/j.nano.2016.05.017","article-title":"Physicochemical properties of core-shell type nanoparticles govern their spatiotemporal biodistribution in the eye","volume":"12","author":"Mahaling","year":"2016","journal-title":"Nanomed. Nanotech. Bio. Med."},{"key":"ref_218","doi-asserted-by":"crossref","unstructured":"Chis, A.A., Dobrea, C., Morgovan, C., Arseniu, A.M., Rus, L.L., Butuca, A., Juncan, A.M., Totan, M., Vonica-Tincu, A.L., and Cormos, G. (2020). Applications and Limitations of Dendrimers in Biomedicine. Molecules, 25.","DOI":"10.3390\/molecules25173982"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1039\/C5BM00532A","article-title":"Stimuli-responsive dendrimers in drug delivery","volume":"4","author":"Wang","year":"2016","journal-title":"Biomater. Sci."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1002\/smll.201303433","article-title":"Topical delivery of Avastin to the posterior segment of the eye in vivo using annexin A5-associated liposomes","volume":"10","author":"Davis","year":"2014","journal-title":"Small"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1097\/IAE.0b013e3181a2f42a","article-title":"Preparation, characterization, and in vivo evaluation of nanoliposomes- encapsulated bevacizumab (avastin) for intravitreal administration","volume":"29","author":"Abrishami","year":"2009","journal-title":"Retina"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ejpb.2022.02.010","article-title":"Lactoferrin-loaded nanostructured lipid carriers (NLCs) as a new formulation for optimized ocular drug delivery","volume":"172","author":"Regueiro","year":"2022","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"374","DOI":"10.4103\/0110-5558.76435","article-title":"Niosome: A future of targeted drug delivery systems","volume":"1","author":"Kazi","year":"2010","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1021\/acs.molpharmaceut.5b00422","article-title":"Protamine\/DNA\/niosome ternary nonviral vectors for gene delivery to the retina: The role of protamine","volume":"12","author":"Puras","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_225","first-page":"2263","article-title":"Ocular and systemic bio-distribution of rhodamine-conjugated liposomes loaded with VIP injected into the vitreous of Lewis rats","volume":"13","author":"Camelo","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.jconrel.2012.01.019","article-title":"Liposomes for intravitreal drug delivery: A state of the art","volume":"161","author":"Bochot","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"863734","DOI":"10.1155\/2011\/863734","article-title":"Recent applications of liposomes in ophthalmic drug delivery","volume":"2011","author":"Mishra","year":"2011","journal-title":"J. Drug. Deliv."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.ijpharm.2004.03.013","article-title":"In vivo gene transfection via intravitreal injection of cationic liposome\/plasmid DNA complexes in rabbits","volume":"278","author":"Kawakami","year":"2004","journal-title":"Int. J. Pharm."},{"key":"ref_229","first-page":"253","article-title":"Intravitreal delivery of oligonucleotides by sterically stabilized liposomes","volume":"43","author":"Bochot","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Ben-Arzi, A., Ehrlich, R., and Neumann, R. (2022). Retinal Diseases: The Next Frontier in Pharmacodelivery. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14050904"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jconrel.2017.01.012","article-title":"Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies","volume":"48","author":"Mandal","year":"2017","journal-title":"J. Control. Release."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3109\/02652048.2015.1134685","article-title":"Optimization of novel pentablock copolymer based composite formulation for sustained delivery of peptide\/protein in the treatment of ocular diseases","volume":"33","author":"Patel","year":"2016","journal-title":"J. Microencapsul."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.biomaterials.2016.08.045","article-title":"Inhibition of VEGF mediated corneal neovascularization by anti-angiogenic peptide nanofibers","volume":"107","author":"Senturk","year":"2016","journal-title":"Biomaterials"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1208\/s12249-014-0196-6","article-title":"Novel pentablock copolymer-based nanoparticulate systems for sustained protein delivery","volume":"16","author":"Patel","year":"2015","journal-title":"AAPS PharmSciTech."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"40174","DOI":"10.1155\/2014\/401747","article-title":"Tailor-made pentablock copolymer based formulation for sustained ocular delivery of protein therapeutics","volume":"2014","author":"Patel","year":"2014","journal-title":"J. Drug Deliv."},{"key":"ref_236","first-page":"5032","article-title":"Nanowafer drug delivery to treat corneal neovascularization","volume":"56","author":"Acharya","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Roman, V.M., Peter, W.J.M., Fraser, S., and Vitaliy, V.K. (2019). Penetration Enhancers in Ocular Drug Delivery. Pharmaceutics., 11.","DOI":"10.3390\/pharmaceutics11070321"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"11719","DOI":"10.1038\/srep11719","article-title":"Discovery of a non-cationic cell penetrating peptide derived from membrane-interacting human proteins and its potential as a protein delivery carrier","volume":"5","author":"Young","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1167\/iovs.16-20072","article-title":"Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides","volume":"58","author":"Hill","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1111\/j.1582-4934.2009.00786.x","article-title":"Cell-Penetrating Peptide TAT-Mediated Delivery of Acidic FGF to Retina and Protection against Ischemia-Reperfusion Injury in Rats","volume":"14","author":"Wang","year":"2010","journal-title":"J. Cell. Mol. Med."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1021\/mp400681n","article-title":"Penetratin, a Potentially Powerful Absorption Enhancer for Noninvasive Intraocular Drug Delivery","volume":"11","author":"Liu","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1034\/j.1399-3011.2000.00723.x","article-title":"Polyarginine Enters Cells More Efficiently than Other Polycationic Homopolymers","volume":"56","author":"Mitchell","year":"2000","journal-title":"J. Pept. Res."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"16010","DOI":"10.1074\/jbc.272.25.16010","article-title":"A Truncated HIV-1 Tat Protein Basic Domain Rapidly Translocates through the Plasma Membrane and Accumulates in the Cell Nucleus","volume":"272","author":"Brodin","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.2147\/IJN.S126865","article-title":"Topical Ocular Delivery to Laser-Induced Choroidal Neovascularization by Dual Internalizing RGD and TAT Peptide-Modified Nanoparticles","volume":"12","author":"Chu","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1016\/j.bbagen.2016.05.031","article-title":"Tat PTD-Endostatin-RGD: A Novel Protein with Anti-Angiogenesis Effect in Retina via Eye Drops. Biochim","volume":"1860","author":"Li","year":"2016","journal-title":"Biophys. Acta Gen. Subj."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"14093","DOI":"10.1073\/pnas.1002713107","article-title":"Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic","volume":"107","author":"Bird","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1039\/C4MD00131A","article-title":"Towards understanding cell penetration by stapled peptides","volume":"6","author":"Chu","year":"2015","journal-title":"Med. Chem. Comm."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1016\/j.vaccine.2004.09.037","article-title":"Conformational constraints imposed on a pan-neutralizing HIV-1 antibody epitope result in increased antigenicity but not neutralizing response","volume":"23","author":"Ho","year":"2005","journal-title":"Vaccine"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.jconrel.2017.09.036","article-title":"High-Density Lipoprotein Mutant Eye Drops for the Treatment of Posterior Eye Diseases","volume":"266","author":"Suda","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ijpharm.2017.06.090","article-title":"A Novel Penetratin-Modified Complex for Noninvasive Intraocular Delivery of Antisense Oligonucleotides","volume":"529","author":"Tai","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.actbio.2017.09.023","article-title":"Discerning the Composition of Penetratin for Safe Penetration from Cornea to Retina","volume":"63","author":"Jiang","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_252","first-page":"506","article-title":"NT-501: An ophthalmic implant of polymer-encapsulated ciliary neurotrophic factor-producing cells","volume":"10","author":"Emerich","year":"2008","journal-title":"Curr. Opin. Mol. Ther."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2165\/11530970-000000000-00000","article-title":"Biodegradable intraocular therapies for retinal disorders: Progress to date","volume":"27","author":"Kuno","year":"2010","journal-title":"Drugs Aging"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"49","DOI":"10.15171\/bi.2016.07","article-title":"Advanced drug delivery and targeting technologies for the ocular diseases","volume":"6","author":"Barar","year":"2016","journal-title":"BioImpacts"},{"key":"ref_255","doi-asserted-by":"crossref","unstructured":"Belhaj, M., Annamalai, B., Parsons, N., Shuler, A., Potts, J., and Rohrer, B. Encapsulated Cell Technology for the Delivery of Biologics to the Mouse Eye. J. Vis. Exp., 2020.","DOI":"10.3791\/60162"},{"key":"ref_256","first-page":"370","article-title":"The use of Matrigel combined with encapsulated cell technology to deliver a complement inhibitor in a mouse model of choroidal neovascularization","volume":"26","author":"Annamalai","year":"2020","journal-title":"Mol. Vis."},{"key":"ref_257","first-page":"360","article-title":"Transcorneal and transscleral iontophoresis of the dexamethasone phosphate into the rabbit eye","volume":"63","author":"Rehak","year":"2007","journal-title":"Cesk. Slov. Oftalmol."},{"key":"ref_258","first-page":"344","article-title":"Methylprednisolone delivery to the back of the eye using hydrogel iontophoresis","volume":"24","author":"Orucov","year":"2008","journal-title":"J. Ocul. Pharmacol. Ther. Off. J. Assoc. Ocul. Pharmacol. Ther."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1080\/02713680701871140","article-title":"In vitro and in vivo evaluation of carboplatin delivery to the eye using hydrogel-iontophoresis","volume":"33","author":"Domb","year":"2008","journal-title":"Curr. Eye Res."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1080\/02713680701528674","article-title":"Methotrexate delivery to the eye using transscleral hydrogel iontophoresis","volume":"32","author":"Domb","year":"2007","journal-title":"Curr. Eye Res."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1089\/jop.2019.0081","article-title":"Transscleral Iontophoresis for Noninvasive Ocular Drug Delivery of Macromolecules","volume":"36","author":"Molokhia","year":"2020","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"011911","DOI":"10.1063\/1.4942516","article-title":"A flexible device for ocular iontophoretic drug delivery","volume":"10","author":"Zhang","year":"2016","journal-title":"Biomicrofluidics"},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1089\/108076803321637672","article-title":"Tolerance of ocular iontophoresis in healthy volunteers","volume":"19","author":"Parkinson","year":"2003","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1089\/108076802321021090","article-title":"in vivo transscleral iontophoresis of amikacin to rabbit eyes","volume":"18","author":"Vollmer","year":"2002","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.jconrel.2005.05.020","article-title":"Transcorneal and transscleral iontophoresis of dexamethasone phosphate using drug loaded hydrogel","volume":"106","author":"Eljarrat","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_266","doi-asserted-by":"crossref","unstructured":"Stanley, T.C., Liang, X.H., Brenda, F.B., and Rosanne, M.C. (2021). Antisense technology: A review. J. Bio. Chem., 296.","DOI":"10.1016\/j.jbc.2021.100416"},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.3762\/bjnano.13.98","article-title":"Microneedle-based ocular drug delivery systems\u2014Recent advances and challenges","volume":"13","author":"Froelich","year":"2022","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1111\/jphp.12152","article-title":"Microneedle- mediated intrascleral delivery of in situ forming thermoresponsive implants for sustained ocular drug delivery","volume":"66","author":"Thakur","year":"2014","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jconrel.2015.04.041","article-title":"Impact insertion of transfer-molded microneedle for localized and minimally invasive ocular drug delivery","volume":"209","author":"Song","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_270","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Estrada, P., Garc\u00eda-Bon, M.A., L\u00f3pez-Naranjo, E.J., Basald\u00faa-P\u00e9rez, D.N., Santos, A., and Navarro-Partida, J. (2021). Polymeric Implants for the Treatment of Intraocular Eye Diseases: Trends in Biodegradable and Non-Biodegradable Materials. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13050701"},{"key":"ref_271","doi-asserted-by":"crossref","unstructured":"Procopio, A., Lagreca, E., Jamaledin, R., La Manna, S., Corrado, B., Di Natale, C., and Onesto, V. (2022). Recent Fabrication Methods to Produce Polymer-Based Drug Delivery Matrices (Experimental and In Silico Approaches). Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14040872"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1089\/jop.2012.0069","article-title":"Indomethacin-loaded solid lipid nanoparticles for ocular delivery: Development, characterization, and In vitro evaluation","volume":"29","author":"Hippalgaonkar","year":"2013","journal-title":"J. Ocu. Pharmacol. Ther."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1016\/j.addr.2005.09.005","article-title":"Intraocular sustained drug delivery using implantable polymeric devices","volume":"57","author":"Yasukawa","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1097\/IAE.0000000000001369","article-title":"Safety of intravitreal Dexamethasone implant (OZURDEX): The SAFODEX study. Incidence and Risk Factors of Ocular Hypertension","volume":"37","author":"Malcles","year":"2017","journal-title":"Retina"},{"key":"ref_275","first-page":"126463","article-title":"Intravitreal devices for the treatment of vitreous inflammation","volume":"2012","author":"Christoforidis","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1016\/j.bcp.2010.07.012","article-title":"On the Retinal Toxicity of Intraocular Glucocorticoids","volume":"80","author":"Torriglia","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.2147\/OPTH.S79948","article-title":"Dexamethasone Intravitreal Implant in the Treatment of Diabetic Macular Edema","volume":"9","author":"Dugel","year":"2015","journal-title":"Clin. Ophthalmol."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0168-3659(98)00061-3","article-title":"Development of a multiple-drug delivery implant for intraocular management of proliferative vitreoretinopathy","volume":"55","author":"Zhou","year":"1998","journal-title":"J. Control. Release"},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.addr.2006.07.026","article-title":"Intraocular implants for extended drug delivery: Therapeutic applications","volume":"58","author":"Bourges","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1097\/IAE.0b013e31817d8bf2","article-title":"Outcome of fluocinolone acetonide implant (Retisert) reimplantation for chronic noninfectious posterior uveitis","volume":"28","author":"Taban","year":"2008","journal-title":"Retina"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.ophtha.2006.02.021","article-title":"Fluocinolone Acetonide Uveitis Study, Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: Thirty-four-week results of a multicenter randomized clinical study","volume":"113","author":"Jaffe","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_282","first-page":"1186","article-title":"Transscleral delivery of bioactive protein to the choroid and retina","volume":"41","author":"Ambati","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.drudis.2013.01.013","article-title":"Injectable implants for the sustained release of protein and peptide drugs","volume":"18","author":"Agarwal","year":"2013","journal-title":"Drug Disc. Today"},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"54","DOI":"10.2174\/1874364101206010054","article-title":"Controlled release of bevacizumab through nanospheres for extended treatment of age-related macular degeneration","volume":"6","author":"Li","year":"2012","journal-title":"Open Ophthalmol. J."},{"key":"ref_285","first-page":"653","article-title":"Pharmacokinetics, and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits","volume":"8","author":"Ye","year":"2015","journal-title":"Int. J. Ophthalmol."},{"key":"ref_286","first-page":"456","article-title":"Nanostructured Porous Silicon Dioxide Microparticles as an Intravitreal Injectable Drug Delivery System for Avastin (Bevacizumab) Lasting Six Months","volume":"53","author":"Freeman","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.ejps.2013.07.014","article-title":"The protective effect of albumin on bevacizumab activity and stability in PLGA nanoparticles intended for retinal and choroidal neovascularization treatments","volume":"50","author":"Varshochian","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.2147\/IJN.S108452","article-title":"Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage","volume":"11","author":"Jeong","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1002\/jbm.a.35446","article-title":"Albuminated PLGA nanoparticles containing bevacizumab intended for ocular neovascularization treatment","volume":"103","author":"Varshochian","year":"2015","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"118217","DOI":"10.1016\/j.carbpol.2021.118217","article-title":"Chitosan coated nanoparticles for efficient delivery of bevacizumab in the posterior ocular tissues via subconjunctival administration","volume":"267","author":"Pandit","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1002\/jbm.a.36424","article-title":"Ocular implant containing Bevacizumab-loaded chitosan nanoparticles intended for choroidal neovascularization treatment","volume":"106","author":"Badiee","year":"2018","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_292","first-page":"36","article-title":"Sustained connexin43 mimetic peptide release from loaded nanoparticles reduces retinal and choroidal photodamage","volume":"59","author":"Guo","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.biopha.2018.08.092","article-title":"Effect of nanoencapsulation using poly (lactide-co- glycolide) (PLGA) on anti-angiogenic activity of bevacizumab for ocular angiogenesis therapy","volume":"107","author":"Zhang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1021\/acs.molpharmaceut.6b01029","article-title":"Hyaluronic acid coated albumin nanoparticles for targeted peptide delivery to the retina","volume":"14","author":"Huang","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_295","first-page":"1","article-title":"Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats","volume":"7","author":"Lu","year":"2014","journal-title":"Int. J. Ophthalmol."},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jconrel.2009.10.031","article-title":"Nanoparticle-integrin antagonist C16Y peptide treatment of choroidal neovascularization in rats","volume":"142","author":"Kim","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_297","first-page":"1637","article-title":"Preclinical development and ocular biodistribution of gemini-DNA nanoparticles after intravitreal and topical administration: Towards non-invasive glaucoma gene therapy. Nanomed. Nanotechnol","volume":"10","author":"Alqawlaq","year":"2014","journal-title":"Biol. Med."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ejpb.2012.09.010","article-title":"Low molecular weight oligochitosans for non-viral retinal gene therapy","volume":"83","author":"Puras","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/gt.2009.158","article-title":"Inhibitory efficacy of hypoxia-inducible factor 1a short hairpin RNA plasmid DNA-loaded poly (D,L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model","volume":"17","author":"Zhang","year":"2010","journal-title":"Gene Ther."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.2337\/db08-1327","article-title":"Nanoparticle-mediated expression of an angiogenic inhibitor ameliorates ischemia-induced retinal neovascularization and diabetes-induced retinal vascular leakage","volume":"58","author":"Park","year":"2009","journal-title":"Diabetes"},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"15461","DOI":"10.1039\/C7NR03142D","article-title":"Therapeutic effects of a novel siRNA-based anti-VEGF (siVEGF) nanoball for the treatment of choroidal neovascularization","volume":"9","author":"Ryoo","year":"2017","journal-title":"Nanoscale"},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1111\/jphp.12940","article-title":"Hyaluronic acid-modified cationic niosomes for ocular gene delivery: Improving transfection efficiency in retinal pigment epithelium","volume":"70","author":"Qin","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"4789","DOI":"10.1167\/iovs.10-5891","article-title":"A lipid nanoparticle system improves siRNA efficacy in RPE cells and a laser-induced murine CNV model","volume":"52","author":"Liu","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.biomaterials.2016.03.004","article-title":"Structural recovery of the retina in a retinoschisin- deficient mouse after gene replacement therapy by solid lipid nanoparticles","volume":"90","author":"Apaolaza","year":"2016","journal-title":"Biomaterials"},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1080\/10717544.2022.2048134","article-title":"Sorafenib-loaded nanostructured lipid carriers for topical ocular therapy of corneal neovascularization: Development, in vitro and in vivo study","volume":"29","author":"Luo","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1039\/D0BM01599G","article-title":"Dasatinib loaded nanostructured lipid carriers for effective treatment of corneal neovascularization","volume":"9","author":"Li","year":"2021","journal-title":"Biomater Sci."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1038\/sj.gt.3302579","article-title":"Dendrimer delivery of an anti-VEGF oligonucleotide into the eye: A long-term study into inhibition of laser induced CNV, distribution, uptake, and toxicity","volume":"12","author":"Marano","year":"2005","journal-title":"Gene Ther."},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1080\/10717544.2018.1474967","article-title":"Multivesicular liposomes for sustained release of bevacizumab in treating laser-induced choroidal neovascularization","volume":"25","author":"Mu","year":"2018","journal-title":"Drug. Deliv."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s13346-016-0298-7","article-title":"In vivo and in vitro sustained release of ranibizumab from a nanoporous thin-film device","volume":"6","author":"Lance","year":"2016","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1167\/tvst.3.6.5","article-title":"Implantable Micropump for Drug Delivery in Patients with Diabetic Macular Edema. Transl","volume":"3","author":"Humayun","year":"2014","journal-title":"Vis. Sci. Tech."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"780634","DOI":"10.1155\/2013\/780634","article-title":"Drug delivery implants in the treatment of vitreous inflammation","volume":"2013","author":"Wang","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/eye.2015.115","article-title":"New and emerging technologies for the treatment of inherited retinal diseases: A horizon scanning review","volume":"29","author":"Smith","year":"2015","journal-title":"Eye"},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1136\/bjophthalmol-2014-306002","article-title":"One year results of a phase 1 study of the safety and tolerability of combination therapy using sustained release intravitreal triamcinolone acetonide and ranibizumab for subfoveal neovascular AMD","volume":"99","author":"Lim","year":"2015","journal-title":"Brit. J. Ophthalmol."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ejpb.2015.07.024","article-title":"Diels-Alder hydrogels with enhanced stability: First step toward controlled release of bevacizumab","volume":"96","author":"Kirchhof","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"6241","DOI":"10.1073\/pnas.1018987108","article-title":"Ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for treatment of geographic atrophy in age-related macular degeneration","volume":"108","author":"Zhang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.biomaterials.2018.03.034","article-title":"Hyaluronic acid coated albumin nanoparticles for targeted peptide delivery in the treatment of retinal ischaemia","volume":"168","author":"Huang","year":"2018","journal-title":"Biomaterials"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/1\/205\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:01:48Z","timestamp":1760119308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/1\/205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,6]]},"references-count":316,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["pharmaceutics15010205"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15010205","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,6]]}}}