{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:06:04Z","timestamp":1786640764076,"version":"build-2736575974"},"reference-count":72,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Exposure to sunlight and contact with atmospheric oxygen makes the eye particularly susceptible to oxidative stress, which can potentially produce cellular damage. In physiological conditions, there are several antioxidant defense mechanisms within the eye. Glutathione (GSH) is the most important antioxidant in the eye; GSH deficit has been linked to several ocular pathologies. The aim of this study was to explore the potential for newly developed formulations allowing controlled delivery of antioxidants such as GSH and vitamin C (Vit C) directly to the eye. We have investigated the stability of antioxidants in aqueous solution and assessed ex-vivo the diffusion of GSH through two ocular membranes, namely cornea and sclera, either in solution or included in a semisolid insert. We have also carried out the hen\u2019s egg-chlorioallantoic membrane test (HET-CAM) to evaluate the ocular irritancy of the different antioxidant solutions. Our results showed that GSH is stable for up to 30 days at 4 \u00b0C in darkness and it is not an irritant to the eye. The diffusion studies revealed that the manufactured formulation, a semisolid insert containing GSH, could deliver this tripeptide directly to the eye in a sustained manner.<\/jats:p>","DOI":"10.3390\/pharmaceutics12090861","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T22:58:01Z","timestamp":1599778681000},"page":"861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Ex-Vivo Trans-Corneal and Trans-Scleral Diffusion Studies with Ocular Formulations of Glutathione as an Antioxidant Treatment for Ocular Diseases"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5914-0516","authenticated-orcid":false,"given":"Mar\u00eda","family":"Sebasti\u00e1n-Morell\u00f3","sequence":"first","affiliation":[{"name":"Facultad de Ciencias de la Salud, Instituto de Ciencias Biom\u00e9dicas, Universidad Cardenal Herrera-CEU, CEU Universities, C\/Santiago Ram\u00f3n y Cajal, s\/n., Alfara del Patriarca, 46115 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9642-1998","authenticated-orcid":false,"given":"Adri\u00e1n M.","family":"Alambiaga-Caravaca","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Instituto de Ciencias Biom\u00e9dicas, Universidad Cardenal Herrera-CEU, CEU Universities, C\/Santiago Ram\u00f3n y Cajal, s\/n., Alfara del Patriarca, 46115 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Aracely","family":"Calatayud-Pascual","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Instituto de Ciencias Biom\u00e9dicas, Universidad Cardenal Herrera-CEU, CEU Universities, C\/Santiago Ram\u00f3n y Cajal, s\/n., Alfara del Patriarca, 46115 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9460-7505","authenticated-orcid":false,"given":"Vicent","family":"Rodilla","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Instituto de Ciencias Biom\u00e9dicas, Universidad Cardenal Herrera-CEU, CEU Universities, C\/Santiago Ram\u00f3n y Cajal, s\/n., Alfara del Patriarca, 46115 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Balaguer-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Instituto de Ciencias Biom\u00e9dicas, Universidad Cardenal Herrera-CEU, CEU Universities, C\/Santiago Ram\u00f3n y Cajal, s\/n., Alfara del Patriarca, 46115 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Miranda","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Instituto de Ciencias Biom\u00e9dicas, Universidad Cardenal Herrera-CEU, CEU Universities, C\/Santiago Ram\u00f3n y Cajal, s\/n., Alfara del Patriarca, 46115 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0601-1440","authenticated-orcid":false,"given":"Alicia","family":"L\u00f3pez-Castellano","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Instituto de Ciencias Biom\u00e9dicas, Universidad Cardenal Herrera-CEU, CEU Universities, C\/Santiago Ram\u00f3n y Cajal, s\/n., Alfara del Patriarca, 46115 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1016\/0002-9343(91)90281-2","article-title":"Oxidative stress: From basic research to clinical application","volume":"91","author":"Sies","year":"1991","journal-title":"Am. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vizzarri, F., Palazzo, M., Bartollino, S., Casamassima, D., Parolini, B., Troiano, P., Caruso, C., and Costagliola, C. (2018). Effects of an Antioxidant Protective Topical Formulation on Eye Exposed to Ultraviolet-Irradiation: A Study in Rabbit Animal Model. Physiol. Res., 457\u2013464.","DOI":"10.33549\/physiolres.933759"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S1542-0124(12)70185-4","article-title":"Antioxidant Defenses in the ocular surface","volume":"7","author":"Chen","year":"2009","journal-title":"Ocul. Surf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/207250","article-title":"Antioxidant Delivery Pathways in the Anterior Eye","volume":"2013","author":"Umapathy","year":"2013","journal-title":"Biomed Res. Int."},{"key":"ref_5","first-page":"94","article-title":"Glutathione in the aqueous humor of human and other species","volume":"19","author":"Riley","year":"1980","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","first-page":"1681","article-title":"Ascorbic acid content of human corneal epithelium","volume":"41","author":"Brubaker","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1089\/jop.2017.0025","article-title":"The Effect of Ascorbic Acid (Vitamin C) on Transepithelial Corneal Cross-Linking in Rabbits","volume":"33","author":"Koc","year":"2017","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Braakhuis, A., Raman, R., and Vaghefi, E. (2017). The Association between Dietary Intake of Antioxidants and Ocular Disease. Diseases, 5.","DOI":"10.3390\/diseases5010003"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1146\/annurev.bi.52.070183.003431","article-title":"Glutathione","volume":"52","author":"Meister","year":"1983","journal-title":"Annu. Rev. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev.pa.25.040185.003435","article-title":"The regulation of hepatic glutathione","volume":"25","author":"Kaplowitz","year":"1985","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1146\/annurev.bi.45.070176.003015","article-title":"Glutathione and Related \u03b3-Glutamyl Compounds: Biosynthesis and Utilization","volume":"45","author":"Meister","year":"1976","journal-title":"Annu. Rev. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.mam.2008.08.004","article-title":"Plasma membrane glutathione transporters and their roles in cell physiology and pathophysiology","volume":"30","author":"Ballatori","year":"2009","journal-title":"Mol. Asp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s10522-013-9463-2","article-title":"Role of antioxidant enzymes and small molecular weight antioxidants in the pathogenesis of age-related macular degeneration (AMD)","volume":"14","author":"Tokarz","year":"2013","journal-title":"Biogerontology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000328979","article-title":"M\u00fcller glial cells in retinal disease","volume":"227","author":"Bringmann","year":"2012","journal-title":"Ophthalmologica"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.freeradbiomed.2016.04.195","article-title":"Alterations in glutamate cysteine ligase content in the retina of two retinitis pigmentosa animal models","volume":"96","author":"Almansa","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.exer.2016.06.018","article-title":"Lens glutathione homeostasis: Discrepancies and gaps in knowledge standing in the way of novel therapeutic approaches","volume":"156","author":"Fan","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1177\/106002809502901213","article-title":"Glutathione in health and disease: Pharmacotherapeutic issues","volume":"29","author":"Lomaestro","year":"1995","journal-title":"Ann. Pharmacother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.1016\/j.bbagen.2012.11.018","article-title":"Glutathione transporters","volume":"1830","author":"Bachhawat","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108026","DOI":"10.1016\/j.neuropharm.2020.108026","article-title":"Oral glutathione administration inhibits the oxidative stress and the inflammatory responses in AppNL-G-F\/NL-G-F knock-in mice","volume":"168","author":"Izumi","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/ejcn.2017.132","article-title":"Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function","volume":"72","author":"Sinha","year":"2018","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3233\/JPD-161040","article-title":"Phase IIb Study of Intranasal Glutathione in Parkinson\u2019s Disease","volume":"7","author":"Mischley","year":"2017","journal-title":"J. Parkinsons Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.neuroscience.2006.12.034","article-title":"Significant photoreceptor rescue by treatment with a combination of antioxidants in an animal model for retinal degeneration","volume":"145","author":"Sanz","year":"2007","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.freeradbiomed.2009.10.042","article-title":"Antioxidants rescue photoreceptors in rd1 mice: Relationship with thiol metabolism","volume":"48","author":"Miranda","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/jphp.12132","article-title":"V Topical delivery of ocular therapeutics: Carrier systems and physical methods","volume":"66","author":"Souza","year":"2014","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1080\/03639040500534101","article-title":"Design and Evaluation of Soluble Ocular Drug Insert for Controlled Release of Ciprofloxacin Hydrochloride","volume":"32","author":"Mundada","year":"2006","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1080\/02713680802023104","article-title":"Formulation and Evaluation of Ciprofloxacin Hydrochloride Soluble Ocular Drug Insert","volume":"33","author":"Mundada","year":"2008","journal-title":"Curr. Eye Res."},{"key":"ref_28","first-page":"164","article-title":"Review on ocular inserts","volume":"1","author":"Rathore","year":"2009","journal-title":"Int. J. Pharm. Tech. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.25004\/IJPSDR.2009.010101","article-title":"An Insight into Ophthalmic Drug Delivery System","volume":"1","author":"Rathore","year":"2009","journal-title":"Int. J. Pharm. Sci. Drug Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/0887-2333(90)90147-L","article-title":"A national validation project of alternative methods to the Draize rabbit eye test","volume":"4","author":"Kalweit","year":"1990","journal-title":"Toxicol. In Vitro"},{"key":"ref_31","first-page":"115","article-title":"Sistemas de liberaci\u00f3n bioadhesivos","volume":"1","author":"Cerezo","year":"2000","journal-title":"ARS Pharm."},{"key":"ref_32","first-page":"1219","article-title":"Design and evaluation of diclofenac sodium ocusert","volume":"1","author":"Ramkanth","year":"2009","journal-title":"Int. J. PharmTech Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2478\/v10007-012-0002-5","article-title":"Design and evaluation of moxifloxacin hydrochloride ocular inserts","volume":"62","author":"Pawar","year":"2012","journal-title":"Acta Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1208\/s12249-008-9139-4","article-title":"Effect of pH and formulation variables on in vitro transcorneal permeability of flurbiprofen: A technical note","volume":"9","author":"Chandran","year":"2008","journal-title":"AAPS PharmSciTech"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ijpharm.2010.04.036","article-title":"Passive asymmetric transport of hesperetin across isolated rabbit cornea","volume":"394","author":"Srirangam","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s13346-017-0443-y","article-title":"Ex vivo rabbit cornea diffusion studies with a soluble insert of moxifloxacin","volume":"8","author":"Rodilla","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1136\/bjo.52.9.695","article-title":"Donor corneae for preservation. A modified dissection technique","volume":"52","author":"Kalevar","year":"1968","journal-title":"Br. J. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.3109\/03639048609063190","article-title":"In Vitro Rabbit Corneal Permeability Study of Ketorolac, Tromethamine, a non-Steroidal Anti-Inflammatory Agent","volume":"12","author":"Fu","year":"1986","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1007\/s11095-008-9730-0","article-title":"Transcorneal permeation of L- and D-aspartate ester prodrugs of acyclovir: Delineation of passive diffusion versus transporter involvement","volume":"26","author":"Majumdar","year":"2009","journal-title":"Pharm. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"423","DOI":"10.5650\/jos.59.423","article-title":"Preparation of Ophthalmic Formulations Containing Cilostazol as an Anti-glaucoma Agent and Improvement in Its Permeability through the Rabbit Cornea","volume":"59","author":"Okamoto","year":"2010","journal-title":"J. Oleo Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0003-2697(80)90118-9","article-title":"High-performance liquid chromatography analysis of nanomole levels of glutathione, glutathione disulfide, and related thiols and disulfides","volume":"106","author":"Reed","year":"1980","journal-title":"Anal. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Alambiaga-Caravaca, A.M., Calatayud-Pascual, M.A., Rodilla, V., Concheiro, A., L\u00f3pez-Castellano, A., and Alvarez-Lorenzo, C. (2020). Micelles of Progesterone for Topical Eye Administration: Interspecies and Intertissues Differences in Ex Vivo Ocular Permeability. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12080702"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lorenzo-Veiga, B., Sigurdsson, H.H., Loftsson, T., and Alvarez-Lorenzo, C. (2019). Cyclodextrin\u2014Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin. Nanomaterials, 9.","DOI":"10.3390\/nano9050745"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0891-5849(02)01304-7","article-title":"Vitamin C and vitamin E restore the resistance of GSH-depleted lens cells to H2O2","volume":"34","author":"Shang","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4887","DOI":"10.1002\/anie.201300399","article-title":"Maillard Degradation Pathways of Vitamin C","volume":"52","author":"Smuda","year":"2013","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_46","first-page":"443","article-title":"Ascorbic acid: Chemistry, biology and the treatment of cancer","volume":"1826","author":"Du","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/BF00386001","article-title":"The presence of glutathione and glutathione reductase in chloroplasts: A proposed role in ascorbic acid metabolism","volume":"133","author":"Foyer","year":"1976","journal-title":"Planta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0891-5849(94)90019-1","article-title":"The redox couple between glutathione and ascorbic acid: A chemical and physiological perspective","volume":"17","author":"Winkler","year":"1994","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/ICO.0b013e31818c901f","article-title":"In Vitro Transcorneal Diffusion of the Antimicrobial Macrolides Azithromycin and Clarithromycin and the Impact on Microbial Keratitis","volume":"28","author":"Seifart","year":"2009","journal-title":"Cornea"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1089\/10807680260362704","article-title":"Comparative permeability of human and rabbit corneas to cyclosporin and tritiated water","volume":"18","author":"Engelbrecht","year":"2002","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_51","unstructured":"Tortora, G.J., and Derrickson, B. (2013). Principios de Anatom\u00eda y Fisiolog\u00eda, Panamerican. [13th ed.]."},{"key":"ref_52","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_53","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jconrel.2004.07.001","article-title":"Model of transient drug diffusion across cornea","volume":"99","author":"Zhang","year":"2004","journal-title":"J. Control. Release"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1159\/000108117","article-title":"Transport barriers in transscleral drug delivery for retinal diseases","volume":"39","author":"Kim","year":"2007","journal-title":"Ophthalmic Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jconrel.2015.02.012","article-title":"Enhanced glutathione PEGylated liposomal brain delivery of an anti-amyloid single domain antibody fragment in a mouse model for Alzheimer\u2019s disease","volume":"203","author":"Rotman","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3109\/1061186X.2014.888070","article-title":"Glutathione PEGylated liposomes: Pharmacokinetics and delivery of cargo across the blood-brain barrier in rats","volume":"22","author":"Rip","year":"2014","journal-title":"J. Drug Target."},{"key":"ref_57","unstructured":"Paquet-Durand, F. (2016, January 1\u20135). Degenerating photoreceptors in Retinitis pigmentosa models release cGMP. A way of self protection?. Proceedings of the Research: A Vision for Hpe ARVO 2016, Seattle, WA, USA."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"291","DOI":"10.4103\/0110-5558.72419","article-title":"Ocular inserts\u2014Advancement in therapy of eye diseases","volume":"1","author":"Kumari","year":"2010","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s11094-015-1269-x","article-title":"Sterilization of Ocular Medical Inserts with Immobilized Proteins","volume":"49","author":"Dekina","year":"2015","journal-title":"Pharm. Chem. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/10717544.2016.1233588","article-title":"Optimizing novel penetration enhancing hybridized vesicles for augmenting the in-vivo effect of an anti-glaucoma drug","volume":"24","author":"Naguib","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_61","first-page":"1733","article-title":"Effect of glutathione ethyl ester, lipoic acid and progesterone on photoreceptor survival in the retina of rd10 mice","volume":"55","author":"Miranda","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.phrs.2015.06.019","article-title":"Neuroprotective actions of progesterone in an in vivo model of retinitis pigmentosa","volume":"99","author":"Romero","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Cant\u00f3, A., Olivar, T., Romero, F.J., and Miranda, M. (2019). Nitrosative Stress in Retinal Pathologies: Review. Antioxidants, 8.","DOI":"10.3390\/antiox8110543"},{"key":"ref_64","first-page":"1","article-title":"Antioxidant therapy in retinitis pigmentosa","volume":"661","author":"Miranda","year":"2010","journal-title":"Nov. Asp. Neuroprot."},{"key":"ref_65","first-page":"700","article-title":"Antioxidants Reduce Cell Death in a Model of Retinitis Pigmentosa: Relationship With Glutathione Metabolism","volume":"50","author":"Gomez","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s12035-008-8045-9","article-title":"Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration","volume":"38","author":"Kustermann","year":"2008","journal-title":"Mol. Neurobiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.1074\/jbc.M111.315705","article-title":"Glutathione Degradation Is a Key Determinant of Glutathione Homeostasis","volume":"287","author":"Lagniel","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"721","DOI":"10.3346\/jkms.2005.20.5.721","article-title":"Pharmacokinetics of Glutathione and Its Metabolites in Normal Subjects","volume":"20","author":"Hong","year":"2005","journal-title":"J. Korean Med. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.preteyeres.2016.12.001","article-title":"Pharmacokinetic aspects of retinal drug delivery","volume":"57","author":"Heikkinen","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.addr.2006.07.025","article-title":"Transscleral drug delivery to the posterior eye: Prospects of pharmacokinetic modeling","volume":"58","author":"Ranta","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s13346-016-0339-2","article-title":"A comprehensive insight on ocular pharmacokinetics","volume":"6","author":"Agrahari","year":"2016","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1089\/jop.2006.22.465","article-title":"Corneal Absorption and Anterior Chamber Pharmacokinetics of Dipeptide Monoester Prodrugs of Ganciclovir (GCV): In Vivo Comparative Evaluation of These Prodrugs with Val-GCV and GCV in Rabbits","volume":"22","author":"Gunda","year":"2006","journal-title":"J. Ocul. Pharmacol. Ther."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/9\/861\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:08:38Z","timestamp":1760177318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/9\/861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,10]]},"references-count":72,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["pharmaceutics12090861"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12090861","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,10]]}}}