{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:14:47Z","timestamp":1773900887944,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["2020.04729.BD"],"award-info":[{"award-number":["2020.04729.BD"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["2020\/04\/X\/ST5\/00789"],"award-info":[{"award-number":["2020\/04\/X\/ST5\/00789"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["START 2021"],"award-info":[{"award-number":["START 2021"]}]},{"name":"National Science Centre within the MINIATURA 4","award":["2020.04729.BD"],"award-info":[{"award-number":["2020.04729.BD"]}]},{"name":"National Science Centre within the MINIATURA 4","award":["2020\/04\/X\/ST5\/00789"],"award-info":[{"award-number":["2020\/04\/X\/ST5\/00789"]}]},{"name":"National Science Centre within the MINIATURA 4","award":["START 2021"],"award-info":[{"award-number":["START 2021"]}]},{"name":"Foundation for Polish Science (FNP)","award":["2020.04729.BD"],"award-info":[{"award-number":["2020.04729.BD"]}]},{"name":"Foundation for Polish Science (FNP)","award":["2020\/04\/X\/ST5\/00789"],"award-info":[{"award-number":["2020\/04\/X\/ST5\/00789"]}]},{"name":"Foundation for Polish Science (FNP)","award":["START 2021"],"award-info":[{"award-number":["START 2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The complexity of the eye structure and its physiology turned ocular drug administration into one of the most challenging topics in the pharmaceutical field. Ocular inflammation is one of the most common ophthalmic disorders. Topical administration of anti-inflammatory drugs is also commonly used as a side treatment in tissue repair and regeneration. The difficulty in overcoming the eye barriers, which are both physical and chemical, reduces drug bioavailability, and the frequency of administration must be increased to reach the therapeutic effect. However, this can cause serious side effects. Lipid nanoparticles seem to be a great alternative to ocular drug delivery as they are composed from natural excipients and can encapsulate both hydrophilic and lipophilic drugs of different sources, and their unique properties, as their excellent biocompatibility, safety and adhesion allow to increase the bioavailability, compliance and achieve a sustained drug release. They are also very stable, easy to produce and scale up, and can be lyophilized or sterilized with no significant alterations to the release profile and stability. Because of this, lipid nanoparticles show a great potential to be an essential part of the new therapeutic technologies in ophthalmology to deliver synthetic and natural anti-inflammatory drugs. In fact, there is an increasing interest in natural bioactives with anti-inflammatory activities, and the use of nanoparticles for their site-specific delivery. It is therefore expected that, in the near future, many more studies will promote the development of new nanomedicines resulting in clinical studies of new drugs formulations.<\/jats:p>","DOI":"10.3390\/ijms232012102","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T22:18:13Z","timestamp":1665526693000},"page":"12102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Lipid-Based Nanoparticulate Systems for the Ocular Delivery of Bioactives with Anti-Inflammatory Properties"],"prefix":"10.3390","volume":"23","author":[{"given":"Raquel da","family":"Ana","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"given":"Joel","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"given":"Jacek","family":"Karczewski","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, Poznan University of Medical Sciences, Fredry 10, 61-701 Poznan, Poland"},{"name":"Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Fredry 10, 61-701 Poznan, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7524-9914","authenticated-orcid":false,"given":"Am\u00e9lia M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Biology and Environment, University of Tr\u00e1s-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal"},{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2603-1377","authenticated-orcid":false,"given":"Aleksandra","family":"Zieli\u0144ska","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, Strzeszy\u0144ska 32, 60-479 Poznan, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-6017","authenticated-orcid":false,"given":"Eliana B.","family":"Souto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"REQUIMTE\/UCIBIO, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3109\/10717544.2010.483257","article-title":"Solid lipid nanoparticles for ocular drug delivery","volume":"17","author":"Seyfoddin","year":"2010","journal-title":"Drug Deliv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3109\/02713681003760168","article-title":"Feasibility of Lipid Nanoparticles for Ocular Delivery of Anti-Inflammatory Drugs","volume":"35","author":"Souto","year":"2010","journal-title":"Curr. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1080\/17425247.2016.1201059","article-title":"Application of lipid nanoparticles to ocular drug delivery","volume":"13","author":"Battaglia","year":"2016","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ejpb.2016.10.013","article-title":"Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye\u2014Part II\u2014Ocular drug-loaded lipid nanoparticles","volume":"110","author":"Espina","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"580118","DOI":"10.3389\/fchem.2021.580118","article-title":"Lipid Nanoparticles as Carriers for Bioactive Delivery","volume":"9","author":"Dhiman","year":"2021","journal-title":"Front. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1089\/jop.2012.0128","article-title":"Lipid nanoparticles as drug\/gene delivery systems to the retina","volume":"29","author":"Delgado","year":"2013","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"288","DOI":"10.4103\/1735-5362.235156","article-title":"Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: Applications, advantages and disadvantages","volume":"13","author":"Ghasemiyeh","year":"2018","journal-title":"Res. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1080\/1061186X.2021.1878366","article-title":"A review of nanocarrier-mediated drug delivery systems for posterior segment eye disease: Challenges analysis and recent advances","volume":"29","author":"Wang","year":"2021","journal-title":"J. Drug Target."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Khiev, D., Mohamed, Z.A., Vichare, R., Paulson, R., Bhatia, S., Mohapatra, S., Lobo, G.P., Valapala, M., Kerur, N., and Passaglia, C.L. (2021). Emerging Nano-Formulations and Nanomedicines Applications for Ocular Drug Delivery. Nanomaterials, 11.","DOI":"10.3390\/nano11010173"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"119831","DOI":"10.1016\/j.ijpharm.2020.119831","article-title":"Cutting-edge advances in therapy for the posterior segment of the eye: Solid lipid nanoparticles and nanostructured lipid carriers","volume":"589","author":"Barbosa","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Fern\u00e1ndez, F.M., Bianchera, A., Gasco, P., Nicoli, S., and Pescina, S. (2021). Lipid-Based Nanocarriers for Ophthalmic Administration: Towards Experimental Design Implementation. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13040447"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27835","DOI":"10.1039\/D0RA04971A","article-title":"Nanocarriers for ocular drug delivery: Current status and translational opportunity","volume":"10","author":"Gorantla","year":"2020","journal-title":"RSC Adv."},{"key":"ref_13","first-page":"7","article-title":"Conventional Opthalamic Drug Delivery System: An Outlook","volume":"1","author":"Madhuvani","year":"2021","journal-title":"Future J. Pharm. Health Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ijpharm.2017.09.017","article-title":"Designing lipid nanoparticles for topical ocular drug delivery","volume":"532","author":"Diebold","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"630352","DOI":"10.3389\/fbioe.2021.630352","article-title":"Update on Nanoparticle-Based Drug Delivery System for Anti-inflammatory Treatment","volume":"9","author":"Wang","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.nano.2009.02.003","article-title":"Nanomedicines for ocular NSAIDs: Safety on drug delivery","volume":"5","author":"Gonzalez","year":"2009","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.plipres.2017.07.001","article-title":"Beyond liposomes: Recent advances on lipid based nanostructures for poorly soluble\/poorly permeable drug delivery","volume":"68","author":"Texeira","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"379","DOI":"10.3390\/jfb6020379","article-title":"Lipid Nanoparticles for Ocular Gene Delivery","volume":"6","author":"Wang","year":"2015","journal-title":"J. Funct. Biomater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejpb.2016.10.009","article-title":"Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye\u2014Part I\u2014Barriers and determining factors in ocular delivery","volume":"110","author":"Espina","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Jacob, S., Nair, A.B., Shah, J., Gupta, S., Boddu, S.H.S., Sreeharsha, N., Joseph, A., Shinu, P., and Morsy, M.A. (2022). Lipid Nanoparticles as a Promising Drug Delivery Carrier for Topical Ocular Therapy\u2014An Overview on Recent Advances. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14030533"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dubashynskaya, N.V., Bokatyi, A.N., Golovkin, A.S., Kudryavtsev, I.V., Serebryakova, M.K., Trulioff, A.S., Dubrovskii, Y.A., and Skorik, Y.A. (2021). Synthesis and Characterization of Novel Succinyl Chitosan-Dexamethasone Conjugates for Potential Intravitreal Dexamethasone Delivery. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222010960"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Dubashynskaya, N.V., Bokatyi, A.N., and Skorik, Y.A. (2021). Dexamethasone Conjugates: Synthetic Approaches and Medical Prospects. Biomedicines, 9.","DOI":"10.3390\/biomedicines9040341"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kickov\u00e1, E., Salmaso, S., Mastrotto, F., Caliceti, P., and Urtti, A. (2021). Pullulan Based Bioconjugates for Ocular Dexamethasone Delivery. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13060791"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ioele, G., Grande, F., De Luca, M., Occhiuzzi, M.A., Garofalo, A., and Ragno, G. (2021). Photodegradation of Anti-Inflammatory Drugs: Stability Tests and Lipid Nanocarriers for Their Photoprotection. Molecules, 26.","DOI":"10.3390\/molecules26195989"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.ajo.2009.05.008","article-title":"Azathioprine for Ocular Inflammatory Diseases","volume":"148","author":"Pasadhika","year":"2009","journal-title":"Am. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1016\/j.ophtha.2009.04.020","article-title":"Methotrexate for Ocular Inflammatory Diseases","volume":"116","author":"Gangaputra","year":"2009","journal-title":"Ophthalmology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1097\/ICU.0b013e3283126d20","article-title":"Immunosuppressive therapy for ocular diseases","volume":"19","author":"Jap","year":"2008","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Dubashynskaya, N., Poshina, D., Raik, S., Urtti, A., and Skorik, Y.A. (2020). Polysaccharides in Ocular Drug Delivery. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12010022"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"118979","DOI":"10.1016\/j.ijpharm.2019.118979","article-title":"Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment","volume":"576","author":"Diebold","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102480","DOI":"10.1016\/j.jddst.2021.102480","article-title":"QbD based development of resveratrol-loaded mucoadhesive lecithin\/chitosan nanoparticles for prolonged ocular drug delivery","volume":"63","author":"Saha","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101765","DOI":"10.1016\/j.jddst.2020.101765","article-title":"Efficiency of nanoparticles for treatment of ocular infections: Systematic literature review","volume":"57","author":"Ghafoorianfar","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tatke, A., Dudhipala, N., Janga, K.Y., Balguri, S.P., Avula, B., Jablonski, M.M., and Majumdar, S. (2019). In Situ Gel of Triamcinolone Acetonide-Loaded Solid Lipid Nanoparticles for Improved Topical Ocular Delivery: Tear Kinetics and Ocular Disposition Studies. Nanomaterials, 9.","DOI":"10.3390\/nano9010033"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"110902","DOI":"10.1016\/j.colsurfb.2020.110902","article-title":"Triamcinolone acetonide loaded-cationic nano-lipoidal formulation for uveitis: Evidences of improved biopharmaceutical performance and anti-inflammatory activity","volume":"190","author":"Nirbhavane","year":"2020","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/02652048.2021.1887383","article-title":"Fluticasone propionate\u2013loaded solid lipid nanoparticles with augmented anti-inflammatory activity: Optimisation, characterisation and pharmacodynamic evaluation on rats","volume":"38","author":"Desoqi","year":"2021","journal-title":"J. Microencapsul."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1080\/10837450.2019.1578370","article-title":"Evaluation of anti-inflammatory impact of dexamethasone-loaded PCL-PEG-PCL micelles on endotoxin-induced uveitis in rabbits","volume":"24","author":"Valizadeh","year":"2019","journal-title":"Pharm. Dev. Technol."},{"key":"ref_36","first-page":"543","article-title":"Preparation and evaluation of celecoxib nanoemulsion for ocular drug delivery","volume":"11","author":"Salimi","year":"2017","journal-title":"Asian J. Pharm. (AJP)"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"105229","DOI":"10.1016\/j.ejps.2020.105229","article-title":"Cationic nanoemulsions with prolonged retention time as promising carriers for ophthalmic delivery of tacrolimus","volume":"144","author":"Zhang","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"118987","DOI":"10.1016\/j.ijpharm.2019.118987","article-title":"Novel Liposome Aggregate Platform (LAP) system for sustained retention of drugs in the posterior ocular segment following intravitreal injection","volume":"576","author":"Blazaki","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","unstructured":"Lan\u00e7on, A., Frazzi, R., and Latruffe, N. (2016). Anti-oxidant, anti-inflammatory and anti-angiogenic properties of resveratrol in ocular diseases. Molecules, 21.","DOI":"10.3390\/molecules21030304"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1080\/03639045.2017.1349787","article-title":"New nanomicelle curcumin formulation for ocular delivery: Improved stability, solubility, and ocular anti-inflammatory treatment","volume":"43","author":"Li","year":"2017","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1080\/10717544.2019.1622608","article-title":"New micelle myricetin formulation for ocular delivery: Improved stability, solubility, and ocular anti-inflammatory treatment","volume":"26","author":"Sun","year":"2019","journal-title":"Drug Deliv."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Giannaccare, G., Pellegrini, M., Senni, C., Bernabei, F., Scorcia, V., and Cicero, A.F.G. (2020). Clinical applications of astaxanthin in the treatment of ocular diseases: Emerging insights. Mar. Drugs, 18.","DOI":"10.3390\/md18050239"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1080\/03639045.2020.1828909","article-title":"New resveratrol micelle formulation for ocular delivery: Characterization and in vitro\/in vivo evaluation","volume":"46","author":"Li","year":"2020","journal-title":"Drug Dev. Ind. Pharm."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12102\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:49:59Z","timestamp":1760143799000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,11]]},"references-count":44,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms232012102"],"URL":"https:\/\/doi.org\/10.3390\/ijms232012102","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,11]]}}}