{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:05:27Z","timestamp":1789441527410,"version":"build-2803163510"},"reference-count":82,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T00:00:00Z","timestamp":1602633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>As an immune-privileged target organ, the eyes have important superficial and internal barriers, protecting them from physical and chemical damage from exogenous and\/or endogenous origins that would cause injury to visual acuity or even vision loss. These anatomic, physiological and histologic barriers are thus a challenge for drug access and entry into the eye. Novel therapeutic concepts are highly desirable for eye treatment. The design of an efficient ocular drug delivery system still remains a challenge. Although nanotechnology may offer the ability to detect and treat eye diseases, successful treatment approaches are still in demand. The growing interest in nanopharmaceuticals offers the opportunity to improve ophthalmic treatments. Besides their size, which needs to be critically monitored, nanopharmaceuticals for ophthalmic applications have to be produced under sterilized conditions. In this work, we have revised the different sterilization and depyrogenation methods for ophthalmic nanopharmaceuticals with their merits and drawbacks. The paper also describes clinical sterilization of drugs and the outcomes of inappropriate practices, while recent applications of nanopharmaceuticals for ocular drug delivery are also addressed.<\/jats:p>","DOI":"10.3390\/biology9100336","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T08:59:22Z","timestamp":1602665962000},"page":"336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Nanopharmaceuticals for Eye Administration: Sterilization, Depyrogenation and Clinical Applications"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2603-1377","authenticated-orcid":false,"given":"Aleksandra","family":"Zieli\u0144ska","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"Institute of Human Genetics, Polish Academy of Sciences, Strzeszy\u0144ska 32, 60-479 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz B.","family":"Soles","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana R.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz F.","family":"Vaz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4725-1897","authenticated-orcid":false,"given":"Camila M.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais F. R.","family":"Alves","sequence":"additional","affiliation":[{"name":"Laboratory of Biomaterial and Nanotechnology (LaBNUS). University of Sorocaba, Raposo Tavares 92.5, Sorocaba, 18078-005 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Klensporf-Pawlik","sequence":"additional","affiliation":[{"name":"Institute of Quality Science, Pozna\u0144 University of Economics and Business, al. Niepodleg\u0142o\u015bci 10, 61-875 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7747-9107","authenticated-orcid":false,"given":"Alessandra","family":"Durazzo","sequence":"additional","affiliation":[{"name":"CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Lucarini","sequence":"additional","affiliation":[{"name":"CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6527-6612","authenticated-orcid":false,"given":"Patricia","family":"Severino","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering, Department of Medicine, Brigham and Women&amp; Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA"},{"name":"Biotechnological Postgraduate Program, University of Tiradentes (Unit), Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil"},{"name":"Institute of Technology and Research (ITP), Nanomedicine and Nanotechnology Laboratory (LNMed), Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil"},{"name":"Tiradentes Institute, 150 Mt Vernon St, Dorchester, MA 02125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-3327","authenticated-orcid":false,"given":"Antonello","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3618-8415","authenticated-orcid":false,"given":"Marco V.","family":"Chaud","sequence":"additional","affiliation":[{"name":"Laboratory of Biomaterial and Nanotechnology (LaBNUS). University of Sorocaba, Raposo Tavares 92.5, Sorocaba, 18078-005 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana B.","family":"Souto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"CEB\u2014Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Baldim, I., Oliveira, W.P., Kadian, V., Rao, R., Yadav, N., Mahant, S., Lucarini, M., Durazzo, A., Da Ana, R., and Capasso, R. (2020). Natural Ergot Alkaloids in Ocular Pharmacotherapy: Known Molecules for Novel Nanoparticle-Based Delivery Systems. Biomolecules, 10.","DOI":"10.3390\/biom10070980"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/s41433-020-0809-0","article-title":"Advances in ocular drug delivery systems","volume":"34","author":"Rudeen","year":"2020","journal-title":"Eye"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.2174\/1381612822666151216145900","article-title":"Ocular Drug Delivery\u2014New Strategies for Targeting Anterior and Posterior Segments of the Eye","volume":"22","author":"Fangueiro","year":"2016","journal-title":"Curr. Pharm. Des."},{"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","unstructured":"Irimia, T., Ghica, M.V., Popa, L., Anu\u0163a, V., Arsene, A.-L., and Dinu-P\u00eervu, C.-E. (2018). Strategies for Improving Ocular Drug Bioavailability and Corneal Wound Healing with Chitosan-Based Delivery Systems. Polymers, 10.","DOI":"10.3390\/polym10111221"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"000222","DOI":"10.15406\/japlr.2016.02.00022","article-title":"Newer Trends in In Situ Gelling Systems for Controlled Ocular Drug Delivery","volume":"2","author":"Jain","year":"2016","journal-title":"J. Anal. Pharm. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.5497\/wjp.v2.i2.47","article-title":"Ocular drug delivery systems: An overview","volume":"2","author":"Patel","year":"2013","journal-title":"World J. Pharmacol."},{"key":"ref_8","first-page":"1","article-title":"Guideline for Hand Hygiene in Health-Care Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC\/SHEA\/APIC\/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America\/Association for Professionals in Infection Control\/Infectious Diseases Society of America","volume":"51","author":"Boyce","year":"2002","journal-title":"MMWR. Recomm. Rep. Morb. Mortal. Wkly. Rep. Recomm. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1128\/CMR.14.3.528-546.2001","article-title":"Nosocomial spread of viral disease","volume":"14","author":"Aitken","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/sj.eye.6702269","article-title":"Tonometers and infectious risk: Myth or reality? Efficacy of different disinfection regimens on tonometer tips","volume":"21","author":"Cillino","year":"2007","journal-title":"Eye"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Souto, E.B., Silva, G.F., Dias-Ferreira, J., Zielinska, A., Ventura, F., Durazzo, A., Lucarini, M., Novellino, E., and Santini, A. (2020). Nanopharmaceutics: Part I\u2014Clinical Trials Legislation and Good Manufacturing Practices (GMP) of Nanotherapeutics in the EU. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020146"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Souto, E.B., Silva, G.F., Dias-Ferreira, J., Zielinska, A., Ventura, F., Durazzo, A., Lucarini, M., Novellino, E., and Santini, A. (2020). Nanopharmaceutics: Part II\u2014Production scales and clinically compliant production methods. Nanomaterials, 10.","DOI":"10.3390\/nano10030455"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Souto, E.B., Sanchez-Lopez, E., Campos, J.R., da Ana, R., Espina, M., Garcia, M.L., Severino, P., Batain, F., Alves, T.F.R., and Crescencio, K.M.M. (2020). Retinal Drug Delivery: Rethinking Outcomes for the Efficient Replication of Retinal Behavior. Appl. Sci., 10.","DOI":"10.3390\/app10124258"},{"key":"ref_14","unstructured":"Kesharwani, P., Taurin, S., and Greish, K. (2020). Polymer nanogels: Fabrication, structural behavior and biological applications. Theory and Applications of Nonparenteral Nanomedicines, Elsevier. Chapter 5."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/smll.200901006","article-title":"Sterilization Matters: Consequences of Different Sterilization Techniques on Gold Nanoparticles","volume":"6","author":"Pelaz","year":"2010","journal-title":"Small"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Dobrovolskaia, M.A., and McNeil, S.E. (2016). Nanoparticle Sterility and Sterilization of Nanomaterials. Handbook of Immunological Properties of Engineered Nanomaterials, World Scientific. [2nd ed.].","DOI":"10.1142\/9677-vol2"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/j.nano.2014.03.017","article-title":"Challenges facing sterilization and depyrogenation of nanoparticles: Effects on structural stability and biomedical applications","volume":"10","author":"Vetten","year":"2014","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_18","first-page":"388","article-title":"Methods of endotoxin removal from biological preparations: A review","volume":"10","author":"Magalhaes","year":"2007","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jain, A., Jain, R., and Jain, S. (2020). Autoclave. Basic Techniques in Biochemistry, Microbiology and Molecular Biology, Springer.","DOI":"10.1007\/978-1-4939-9861-6"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1128\/JCM.02161-16","article-title":"Validation of autoclave protocols for successful decontamination of category a medical waste generated from care of patients with serious communicable diseases","volume":"55","author":"Garibaldi","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"87","DOI":"10.4103\/2230-973X.153383","article-title":"Effect of the moist-heat sterilization on fabricated nanoscale solid lipid particles containing rasagiline mesylate","volume":"5","author":"Viveksarathi","year":"2015","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ijpharm.2008.07.028","article-title":"Cyclosporine A loaded SLNs: Evaluation of cellular uptake and corneal cytotoxicity","volume":"364","author":"Gokce","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.msec.2011.02.004","article-title":"Influence of sterilization methods on cell behavior and functionality of osteoblasts cultured on TiO2 nanotubes","volume":"31","author":"Oh","year":"2011","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_24","first-page":"001","article-title":"Sterilization of Silver Nanoparticles Using Standard Gamma Irradiation Procedure Affects Particle Integrity and Biocompatibility","volume":"2011","author":"Zheng","year":"2011","journal-title":"J. Nanomed. Nanotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1208\/s12248-012-9339-4","article-title":"Challenges in development of nanoparticle-based therapeutics","volume":"14","author":"Desai","year":"2012","journal-title":"AAPS J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ijpharm.2005.12.013","article-title":"Sterile, injectable cyclodextrin nanoparticles: Effects of gamma irradiation and autoclaving","volume":"311","author":"Hincal","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_27","first-page":"1000305","article-title":"A new preparation method for ophthalmic drug nanoparticles","volume":"5","author":"Nagai","year":"2014","journal-title":"Pharm. Anal. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"184","DOI":"10.5731\/pdajpst.2012.00774","article-title":"The effect of radiation on a variety of pharmaceuticals and materials containing polymers","volume":"66","author":"Silindir","year":"2012","journal-title":"PDA J. Pharm. Sci. Technol."},{"key":"ref_29","first-page":"43","article-title":"Sterilization methods and the comparison of e-beam sterilization with gamma radiation sterilization","volume":"34","author":"Silindir","year":"2009","journal-title":"Fabad J. Pharm. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1023\/A:1023267304096","article-title":"The stenlying effect of high hydrostatic pressure on thermally and hydrolytically labile nanosized carriers","volume":"20","author":"Brigger","year":"2003","journal-title":"Pharm. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8769","DOI":"10.3390\/s110908769","article-title":"Gamma-ray sterilization effects in silica nanoparticles\/gamma-APTES nanocomposite-based pH-sensitive polysilicon wire sensors","volume":"11","author":"Lin","year":"2011","journal-title":"Sensors"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0378-5173(97)00394-3","article-title":"Sterilization of unloaded polybutylcyanoacrylate nanoparticles","volume":"164","author":"Sommerfeld","year":"1998","journal-title":"Int. J. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"35","DOI":"10.22159\/ajpcr.2018.v11i7.25149","article-title":"Emerging novel nanopharmaceuticals for drug delivery","volume":"11","author":"Wadhwa","year":"2018","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"274","DOI":"10.7150\/ijms.22644","article-title":"Risks of using sterilization by gamma radiation: The other side of the coin","volume":"15","author":"Harrell","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hume, A.J., Ames, J., Rennick, L.J., Duprex, W.P., Marzi, A., Tonkiss, J., and M\u00fchlberger, E. (2016). Inactivation of RNA viruses by gamma irradiation: A study on mitigating factors. Viruses, 8.","DOI":"10.3390\/v8070204"},{"key":"ref_36","unstructured":"Chen, Y. (2020). Chapter 2\u2014Natural polymers and the hydrogels prepared from them. Hydrogels Based on Natural Polymers, Elsevier."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.toxlet.2020.03.004","article-title":"N-(2-Hydroxyethyl)-L-valyl-L-leucine: A novel urinary biomarker of ethylene oxide exposure in humans","volume":"326","author":"Linhart","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.3762\/bjnano.9.98","article-title":"Review on nanoparticles and nanostructured materials: History, sources, toxicity and regulations","volume":"9","author":"Jeevanandam","year":"2018","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.ejpb.2005.11.007","article-title":"Sterilization of gentamicin containing collagen\/PLGA microparticle composites","volume":"63","author":"Friess","year":"2006","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1351\/pac200274030349","article-title":"Plasma sterilization. Methods and mechanisms","volume":"74","author":"Moisan","year":"2002","journal-title":"Pure Appl. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"731","DOI":"10.3892\/etm.2010.136","article-title":"Gas plasma sterilization of microorganisms and mechanisms of action","volume":"1","author":"Shintani","year":"2010","journal-title":"Exp. Ther. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"555","DOI":"10.2217\/nnm.10.29","article-title":"Ambiguities in applying traditional Limulus amebocyte lysate tests to quantify endotoxin in nanoparticle formulations","volume":"5","author":"Dobrovolskaia","year":"2010","journal-title":"Nanomedicine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1743-8977-9-41","article-title":"Contamination of nanoparticles by endotoxin: Evaluation of different test methods","volume":"9","author":"Smulders","year":"2012","journal-title":"Part. Fibre Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"269","DOI":"10.2217\/nnm.15.196","article-title":"Endotoxin contamination: A key element in the interpretation of nanosafety studies","volume":"11","author":"Li","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3389\/fimmu.2017.00472","article-title":"Endotoxin contamination in nanomaterials leads to the misinterpretation of immunosafety results","volume":"8","author":"Li","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5402\/2012\/649746","article-title":"Chromatographic removal of endotoxins: A bioprocess engineer\u2019s perspective","volume":"2012","author":"Ongkudon","year":"2012","journal-title":"ISRN Chromatogr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"540","DOI":"10.21608\/ejceh.2015.253599","article-title":"Depyrogenation methods","volume":"1","author":"Salama","year":"2015","journal-title":"Egypt. J. Chem. Environ. Health"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.addr.2007.04.007","article-title":"Solid lipid nanoparticles as a drug delivery system for peptides and proteins","volume":"59","author":"Almeida","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ejpb.2016.08.001","article-title":"Preclinical safety of solid lipid nanoparticles and nanostructured lipid carriers: Current evidence from in vitro and in vivo evaluation","volume":"108","author":"Doktorovova","year":"2016","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejpb.2014.02.005","article-title":"Nanotoxicology applied to solid lipid nanoparticles and nanostructured lipid carriers\u2014A systematic review of in vitro data","volume":"87","author":"Doktorovova","year":"2014","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-3-642-00477-3_4","article-title":"Lipid nanoparticles: Effect on bioavailability and pharmacokinetic changes","volume":"197","author":"Souto","year":"2010","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.nano.2011.10.015","article-title":"Release profile and transscleral permeation of triamcinolone acetonide loaded nanostructured lipid carriers (TA-NLC): In vitro and ex vivo studies","volume":"8","author":"Araujo","year":"2012","journal-title":"Nanomedicine"},{"key":"ref_53","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":"Araujo","year":"2009","journal-title":"Nanomedicine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.colsurfb.2010.07.029","article-title":"Design and ocular tolerance of flurbiprofen loaded ultrasound-engineered NLC","volume":"81","author":"Egea","year":"2010","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"045101","DOI":"10.1088\/0957-4484\/22\/4\/045101","article-title":"Optimizing flurbiprofen-loaded NLC by central composite factorial design for ocular delivery","volume":"22","author":"Egea","year":"2011","journal-title":"Nanotechnology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/jps.22784","article-title":"Improved and safe transcorneal delivery of flurbiprofen by NLC and NLC-based hydrogels","volume":"101","author":"Nikolic","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.colsurfb.2011.06.025","article-title":"Nanostructured lipid carriers for triamcinolone acetonide delivery to the posterior segment of the eye","volume":"88","author":"Araujo","year":"2011","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ijpharm.2013.11.025","article-title":"Design of cationic lipid nanoparticles for ocular delivery: Development, characterization and cytotoxicity","volume":"461","author":"Fangueiro","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1080\/17425247.2020.1772750","article-title":"Analytical tools and evaluation strategies for nanostructured lipid carrier based topical delivery systems","volume":"17","author":"Mahant","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/17425247.2020.1727883","article-title":"SLN and NLC for topical, dermal and transdermal drug delivery","volume":"17","author":"Souto","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0378-5173(96)04822-3","article-title":"Sterilization and freeze-drying of drug-free and drug-loaded solid lipid nanoparticles","volume":"148","author":"Cavalli","year":"1997","journal-title":"Int. J. Pharm."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Rafael, D., Andrade, F., Martinez-Trucharte, F., Basas, J., Seras-Franzoso, J., Palau, M., Gomis, X., P\u00e9rez-Burgos, M., Blanco, A., and L\u00f3pez-Fern\u00e1ndez, A. (2019). Sterilization Procedure for Temperature-Sensitive Hydrogels Loaded with Silver Nanoparticles for Clinical Applications. Nanomaterials, 9.","DOI":"10.3390\/nano9030380"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1517\/17425247.2012.665367","article-title":"In situ gel systems as \u2018smart\u2019 carriers for sustained ocular drug delivery","volume":"9","author":"Agrawal","year":"2012","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ajps.2018.04.008","article-title":"Research progress of in-situ gelling ophthalmic drug delivery system","volume":"14","author":"Wu","year":"2019","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.msec.2015.11.034","article-title":"Design and characterization of chitosan\/zeolite composite films\u2014Effect of zeolite type and zeolite dose on the film properties","volume":"60","author":"Barbosa","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Diniz, F.R., Maia, R.C.A.P., Rannier, L., Andrade, L.N., Chaud, M.V., da Silva, C.F., Corr\u00eaa, C.B., de Albuquerque Junior, R.L.C., da Costa, L.P., and Souto, E.B. (2020). Silver nanoparticles-composing alginate\/gelatin hydrogel improves wound healing in vivo. Nanomaterials, 10.","DOI":"10.3390\/nano10020390"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Hissae Yassue-Cordeiro, P., Zandonai, C.H., Pereira Genesi, B., Santos Lopes, P., Sanchez-Lopez, E., Garcia, M.L., Camargo Fernandes-Machado, N.R., Severino, P., Souto, E.B., and Ferreira da Silva, C. (2019). Development of Chitosan\/Silver Sulfadiazine\/Zeolite Composite Films for Wound Dressing. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11100535"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.crbiot.2020.04.002","article-title":"Big impact of nanoparticles: Analysis of the most cited nanopharmaceuticals and nanonutraceuticals research","volume":"2","author":"Yeung","year":"2020","journal-title":"Curr. Res. Biotechnol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1002\/jbm.b.34048","article-title":"Sterilization of hydrogels for biomedical applications: A review","volume":"106","author":"Galante","year":"2018","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-L\u00f3pez, E., Gomes, D., Esteruelas, G., Bonilla, L., Lopez-Machado, A.L., Galindo, R., Cano, A., Espina, M., Ettcheto, M., and Camins, A. (2020). Metal-Based Nanoparticles as Antimicrobial Agents: An Overview. Nanomaterials, 10.","DOI":"10.3390\/nano10020292"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Dutz, S., Wojahn, S., Gr\u00e4fe, C., Weidner, A., and Clement, J.H. (2017). Influence of Sterilization and Preservation Procedures on the Integrity of Serum Protein-Coated Magnetic Nanoparticles. Nanomaterials, 7.","DOI":"10.3390\/nano7120453"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1016\/j.biomaterials.2009.11.103","article-title":"The role of sterilization in the cytocompatibility of titania nanotubes","volume":"31","author":"Zhao","year":"2010","journal-title":"Biomaterials"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/0969-806X(95)00138-N","article-title":"Effects of X-and UV-irradiation on proteins","volume":"47","author":"Durchschlag","year":"1996","journal-title":"Radiat. Phys. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1023\/A:1025040522513","article-title":"Effect of crosslinking, thermal treatment and UV irradiation on the mechanical properties and in vitro degradation behavior of several natural proteins aimed to be used in the biomedical field","volume":"14","author":"Vaz","year":"2003","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"15756","DOI":"10.1021\/ja064884j","article-title":"Toward monodispersed silver nanoparticles with unusual thermal stability","volume":"128","author":"Sun","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1007\/s10856-008-3381-x","article-title":"Sterilization effects on starPEG coated polymer surfaces: Characterization and cell viability","volume":"19","author":"Grafahrend","year":"2008","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.jcrs.2006.01.065","article-title":"Toxic anterior segment syndrome","volume":"32","author":"Mamalis","year":"2006","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.jcrs.2018.05.001","article-title":"Guidelines for the cleaning and sterilization of intraocular surgical instruments","volume":"44","author":"Chang","year":"2018","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.survophthal.2019.01.009","article-title":"Toxic anterior segment syndrome: A review","volume":"64","author":"Navas","year":"2019","journal-title":"Surv. Ophthalmol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.jcrs.2010.01.030","article-title":"Toxic anterior segment syndrome: Common causes","volume":"36","author":"Brubaker","year":"2010","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_81","first-page":"414","article-title":"The preparation and sterilization of ophthalmic solutions","volume":"71","author":"Hogan","year":"1949","journal-title":"Calif. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1248\/yakushi.129.495","article-title":"Stability studies on aqueous and oily ophthalmic solutions of diclofenac","volume":"129","author":"Ahuja","year":"2009","journal-title":"Yakugaku Zasshi"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/9\/10\/336\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:21:12Z","timestamp":1760178072000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/9\/10\/336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,14]]},"references-count":82,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["biology9100336"],"URL":"https:\/\/doi.org\/10.3390\/biology9100336","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,14]]}}}