{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:54:25Z","timestamp":1788926065285,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T00:00:00Z","timestamp":1568419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004770","name":"Universit\u00e0 degli Studi di Parma","doi-asserted-by":"publisher","award":["20173ZECCM"],"award-info":[{"award-number":["20173ZECCM"]}],"id":[{"id":"10.13039\/501100004770","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>This paper addresses the problem of ocular delivery of lipophilic drugs. The aim of the paper is the evaluation of polymeric micelles, prepared using TPGS (d-\u03b1-Tocopheryl polyethylene glycol 1000 succinate), a water-soluble derivative of Vitamin E and\/or poloxamer 407, as a vehicle for the ocular delivery of dexamethasone, cyclosporine, and econazole nitrate. The research steps were: (1) characterize polymeric micelles by dynamic light scattering (DLS) and X-ray scattering; (2) evaluate the solubility increase of the three drugs; (3) measure the in vitro transport and conjunctiva retention, in comparison to conventional vehicles; (4) investigate the mechanisms of enhancement, by studying drug release from the micelles and transconjunctival permeation of TPGS; and (5) study the effect of micelles application on the histology of conjunctiva. The data obtained demonstrate the application potential of polymeric micelles in ocular delivery, due to their ability to increase the solubility of lipophilic drugs and enhance transport in and across the conjunctival epithelium. The best-performing formulation was the one made of TPGS alone (micelles size \u2248 12 nm), probably because of the higher mobility of these micelles, an enhanced interaction with the conjunctival epithelium, and, possibly, the penetration of intact micelles.<\/jats:p>","DOI":"10.3390\/pharmaceutics11090476","type":"journal-article","created":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T03:17:57Z","timestamp":1568603877000},"page":"476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Ex Vivo Conjunctival Retention and Transconjunctival Transport of Poorly Soluble Drugs Using Polymeric Micelles"],"prefix":"10.3390","volume":"11","author":[{"given":"Silvia","family":"Pescina","sequence":"first","affiliation":[{"name":"Department of Food and Drug, University of Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Grolli Lucca","sequence":"additional","affiliation":[{"name":"Department of Food and Drug, University of Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7596-6251","authenticated-orcid":false,"given":"Paolo","family":"Govoni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, via Volturno 39, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Padula","sequence":"additional","affiliation":[{"name":"Department of Food and Drug, University of Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6584-1869","authenticated-orcid":false,"given":"Elena","family":"Del Favero","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies and Translational Medicine, LITA, University of Milan, 20090 Segrate (MI), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cant\u00f9","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies and Translational Medicine, LITA, University of Milan, 20090 Segrate (MI), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7601-7894","authenticated-orcid":false,"given":"Patrizia","family":"Santi","sequence":"additional","affiliation":[{"name":"Department of Food and Drug, University of Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6955-0957","authenticated-orcid":false,"given":"Sara","family":"Nicoli","sequence":"additional","affiliation":[{"name":"Department of Food and Drug, University of Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,14]]},"reference":[{"key":"ref_1","first-page":"627","article-title":"Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera","volume":"38","author":"Hamalainen","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1080\/17425247.2019.1597848","article-title":"Topical application of polymeric nanomicelles in ophthalmology: A review on research efforts for the noninvasive delivery of ocular therapeutics","volume":"16","author":"Grimaudo","year":"2019","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ijpharm.2017.09.005","article-title":"Polymeric micelles: Basic research to clinical practice","volume":"532","author":"Deshmukh","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ijpharm.2018.09.053","article-title":"Soluplus micelles for acyclovir ocular delivery: Formulation and cornea and sclera permeability","volume":"552","author":"Concheiro","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Noh, G., Keum, T., Seo, J.-E., Choi, J., Rakesh, B., Shrawani, L., Park, B., Choi, Y.W., and Lee, S. (2018). Development and Evaluation of a Water Soluble Fluorometholone Eye Drop Formulation Employing Polymeric Micelle. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10040208"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1208\/s12249-014-0100-4","article-title":"Novel dexamethasone-loaded nanomicelles for the intermediate and posterior segment uveitis","volume":"15","author":"Vaishya","year":"2014","journal-title":"AAPS PharmSciTech"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1021\/acs.molpharmaceut.7b00939","article-title":"Poloxamer 407\/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery","volume":"15","author":"Grimaudo","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ijpharm.2009.05.028","article-title":"Polyhydroxyethylaspartamide-based micelles for ocular drug delivery","volume":"378","author":"Civiale","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1038\/sj.gt.3301485","article-title":"In vivo gene delivery into ocular tissues by eye drops of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles","volume":"8","author":"Liaw","year":"2001","journal-title":"Gene Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.ijpharm.2019.06.011","article-title":"Exploring optimized methoxy poly(ethylene glycol)-block-poly(\u03b5-caprolactone) crystalline cored micelles in anti-glaucoma pharmacotherapy","volume":"566","author":"Elmowafy","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1080\/10717544.2019.1568624","article-title":"Ultra-small micelles based on polyoxyl 15 hydroxystearate for ocular delivery of myricetin: Optimization, in vitro, and in vivo evaluation","volume":"26","author":"Hou","year":"2019","journal-title":"Drug Deliv."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","unstructured":"Lorenzo-Veiga, B., Sigurdsson, H.H., Loftsson, T., and Alvarez-Lorenzo, C. (2019). Cyclodextrin\u2013Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin. Nanomaterials, 9.","DOI":"10.3390\/nano9050745"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bongiov\u00ec, F., Di Prima, G., Palumbo, F.S., Licciardi, M., Pitarresi, G., and Giammona, G. (2017). Hyaluronic Acid-Based Micelles as Ocular Platform to Modulate the Loading, Release, and Corneal Permeation of Corticosteroids. Macromol. Biosci., 17.","DOI":"10.1002\/mabi.201700261"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1208\/s12249-017-0714-4","article-title":"Clear, Aqueous Topical Drop of Triamcinolone Acetonide","volume":"18","author":"Trinh","year":"2017","journal-title":"AAPS PharmSciTech"},{"key":"ref_16","first-page":"2921","article-title":"Cyclosporine Amicellar delivery system for dry eyes","volume":"11","author":"Kang","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Holland, E.J., Mannis, M.J., and Lee, W.B. (2013). Conjunctival anatomy and physiology. Ocular Surface Disease: Cornea, Conjunctiva and Tear Film, Elsevier Saunders.","DOI":"10.1016\/B978-1-4557-2876-3.00058-4"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ejps.2018.03.034","article-title":"Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye","volume":"119","author":"Ramsay","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ejpb.2004.12.007","article-title":"Roles of the conjunctiva in ocular drug delivery: A review of conjunctival transport mechanisms and their regulation","volume":"60","author":"Hosoya","year":"2005","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2174\/1874364101711010305","article-title":"A Single Drop in the Eye - Effects on the Whole Body?","volume":"11","author":"Vaajanen","year":"2017","journal-title":"Open Ophthalmol. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/0039-6257(93)90141-S","article-title":"Minimizing systemic absorption of topically administered ophthalmic drugs","volume":"37","author":"Urtti","year":"1993","journal-title":"Surv. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0939-6411(03)00138-3","article-title":"Cyclosporine A delivery to the eye: A pharmaceutical challenge","volume":"56","author":"Lallemand","year":"2003","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1167\/tvst.4.3.1","article-title":"Topical, Aqueous, Clear Cyclosporine Formulation Design for Anterior and Posterior Ocular Delivery","volume":"4","author":"Cholkar","year":"2015","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1136\/bjo.87.10.1235","article-title":"A randomised clinical trial comparing 2% econazole and 5% natamycin for the treatment of fungal keratitis","volume":"87","author":"Prajna","year":"2003","journal-title":"Br. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1089\/jop.2018.0089","article-title":"Challenges in the Polyene- and Azole-Based Pharmacotherapy of Ocular Fungal Infections","volume":"35","author":"Lakhani","year":"2019","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.xphs.2017.12.028","article-title":"Ophthalmic Econazole Hydrogels for the Treatment of Fungal Keratitis","volume":"107","author":"Herranz","year":"2018","journal-title":"J. Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13387","DOI":"10.1038\/s41598-018-31846-z","article-title":"Imidazole Compounds for Protecting Choroidal Endothelial Cells from Complement Injury","volume":"8","author":"Zeng","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1080\/03639045.2017.1318910","article-title":"Mydriatics release from solid and semi-solid ophthalmic formulations using different in vitro methods","volume":"43","author":"Pescina","year":"2017","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_30","unstructured":"Advanced Chemistry Development, Inc. (2019, April 12). ACD\/i-lab, Advanced Chemistry Development 2019. Available online: https:\/\/ilab.acdlabs.com\/iLab2\/."},{"key":"ref_31","unstructured":"Doucet, M., Cho, J.H., Alina, G., Bakker, J., Bouwman, W., Butler, P., Campbell, K., Gonzales, M., Heenan, G., and Jackson, A. (2019). SasView Version 4.2.1, Zenodo."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"571","DOI":"10.3109\/02713689109001766","article-title":"Lipophilicity influence on conjunctival drug penetration in the pigmented rabbit: A comparison with corneal penetration","volume":"10","author":"Wang","year":"1991","journal-title":"Curr. Eye Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/jps.2600760802","article-title":"Physicochemical determinants of drug diffusion across the conjunctiva, sclera, and cornea","volume":"76","author":"Ahmed","year":"1987","journal-title":"J. Pharm. Sci"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.2042-7158.1997.tb06767.x","article-title":"Ocular membrane permeability of hydrophilic drugs for ocular peptide delivery","volume":"49","author":"Sasaki","year":"1997","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1023\/A:1012123411343","article-title":"Polar solute transport across the pigmented rabbit conjunctiva: Size dependence and the influence of 8-bromo cyclic adenosine monophosphate","volume":"14","author":"Horibe","year":"1997","journal-title":"Pharm. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1248\/bpb.23.1524","article-title":"Modification of ocular permeability of peptide drugs by absorption promoters","volume":"23","author":"Sasaki","year":"2000","journal-title":"Biol. Pharm. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3109\/10611869509059212","article-title":"Ocular permeability of FITC-dextran with absorption promoter for ocular delivery of peptide drug","volume":"3","author":"Sasaki","year":"1995","journal-title":"J. Drug Target"},{"key":"ref_38","first-page":"1185","article-title":"Luteinizing hormone-releasing hormone agonist and transferrin functionalizations enhance nanoparticle delivery in a novel bovine ex vivo eye model","volume":"12","author":"Kompella","year":"2006","journal-title":"Mol. Vis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1016\/j.xphs.2017.04.061","article-title":"Impact of Chemical Structure on Conjunctival Drug Permeability: Adopting Porcine Conjunctiva and Cassette Dosing for Construction of In Silico Model","volume":"106","author":"Ramsay","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_40","unstructured":"Ehrhardt, C., and Kim, K.J. (2008). The Conjunctival Barrier in Ocular Drug Delivery. Drug Absorption Studies In Situ, In Vitro and In Silico Models, Springer."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ejps.2013.04.012","article-title":"How do polymeric micelles cross epithelial barriers?","volume":"50","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ejps.2018.04.032","article-title":"Biopharmaceutical evaluation of surface active ophthalmic excipients using in vitro and ex vivo corneal models","volume":"120","author":"Hafner","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_43","first-page":"684","article-title":"Paracellular permeability of corneal and conjunctival epithelia","volume":"30","author":"Huang","year":"1989","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_44","first-page":"518","article-title":"Rheological, mucoadhesive and release properties of pluronic F-127 gel and pluronic F-127\/polycarbophil mixed gel systems","volume":"60","author":"Tirnaksiz","year":"2005","journal-title":"Pharmazie"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4737","DOI":"10.1021\/acs.langmuir.7b00701","article-title":"Structural and Spectroscopic Characterization of TPGS Micelles: Disruptive Role of Cyclodextrins and Kinetic Pathways","volume":"33","author":"Grillo","year":"2017","journal-title":"Langmuir"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.3390\/nano5041766","article-title":"Control of Partial Coalescence of Self-Assembled Metal Nano-Particles across Lyotropic Liquid Crystals Templates towards Long Range Meso-Porous Metal Frameworks Design","volume":"5","author":"Lemoine","year":"2015","journal-title":"Nanomaterials"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1021\/ma702269c","article-title":"Effects of PEO-PPO Diblock Impurities on the Cubic Structure of Aqueous PEO-PPO-PEO Pluronics Micelles: Fcc and bcc Ordered Structures in F127","volume":"41","author":"Mortensen","year":"2018","journal-title":"Macromolecules"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1021\/ma00093a016","article-title":"Phase Diagrams and Aggregation Behavior of Poly(oxyethylene)-Poly(oxypropylene)-Poly(oxyethylene) Triblock Copolymers in Aqueous Solutions","volume":"27","author":"Wanka","year":"1994","journal-title":"Macromolecules"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1039\/a902369k","article-title":"Direct visualisation of micelles of Pluronic block copolymers in aqueous solution by cryo-TEM","volume":"1","author":"Lam","year":"1999","journal-title":"Phys. Chem. Chem. Phys. PCCP"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5555","DOI":"10.2147\/IJN.S213086","article-title":"Superiority of TPGS-loaded micelles in the brain delivery of vinpocetine via administration of thermosensitive intranasal gel","volume":"14","author":"Ahmed","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"769","DOI":"10.3389\/fphar.2019.00769","article-title":"Synthesis of TPGS\/Curcumin Nanoparticles by Thin-Film Hydration and Evaluation of Their Anti-Colon Cancer Efficacy In Vitro and In Vivo","volume":"10","author":"Li","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1021\/mp500711c","article-title":"Evolution of supersaturation of amorphous pharmaceuticals: Nonlinear rate of supersaturation generation regulated by matrix diffusion","volume":"12","author":"Sun","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"704","DOI":"10.3109\/1061186X.2010.525652","article-title":"Using polymeric precipitation inhibitors to improve the absorption of poorly water-soluble drugs: A mechanistic basis for utility","volume":"18","author":"Warren","year":"2010","journal-title":"J. Drug Target"},{"key":"ref_54","first-page":"131","article-title":"Influence of cosolvents, ionic strength and the method of sample preparation on the solubilization of curcumin by Pluronics and HP-gamma-cyclodextrin. Studies of curcumin and curcuminoids, XLIV","volume":"67","author":"Singh","year":"2012","journal-title":"Pharmazie"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s11095-007-9417-y","article-title":"Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing","volume":"25","author":"Overhoff","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1002\/jps.20906","article-title":"Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations","volume":"96","author":"Tawa","year":"2007","journal-title":"J. Pharm. Sci."},{"key":"ref_57","first-page":"1221","article-title":"Existence of a p-glycoprotein drug efflux pump in cultured rabbit conjunctival epithelial cells","volume":"39","author":"Saha","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.addr.2017.12.009","article-title":"Expression, activity and pharmacokinetic impact of ocular transporters","volume":"126","author":"Vellonen","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1023\/A:1007508714259","article-title":"Role of P-glycoprotein in restricting propranolol transport in cultured rabbit conjunctival epithelial cell layers","volume":"17","author":"Yang","year":"2000","journal-title":"Pharm. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ijpharm.2012.09.051","article-title":"Enhancement of corneal permeation of riboflavin-5\u2019-phosphate through vitamin E TPGS: A promising approach in corneal trans-epithelial cross linking treatment","volume":"440","author":"Ostacolo","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Moiseev, R.V., Morrison, P., Steele, F., and Khutoryanskiy, V.V. (2019). Penetration Enhancers in Ocular Drug Delivery. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11070321"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1021\/mp060121r","article-title":"Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: Influence on ATPase activity and membrane fluidity","volume":"4","author":"Collnot","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"861904","DOI":"10.1155\/2014\/861904","article-title":"Ophthalmic drug dosage forms: Characterisation and research methods","volume":"2014","author":"Baranowski","year":"2014","journal-title":"Sci. World J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1080\/10717544.2018.1458923","article-title":"Improving the topical ocular pharmacokinetics of lyophilized cyclosporine A-loaded micelles: Formulation, in vitro and in vivo studies","volume":"25","author":"Yu","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ejpb.2017.05.005","article-title":"Novel inulin-based mucoadhesive micelles loaded with corticosteroids as potential transcorneal permeation enhancers","volume":"117","author":"Saladino","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ejpb.2012.02.014","article-title":"Novel micelle carriers for cyclosporin A topical ocular delivery: In vivo cornea penetration, ocular distribution and efficacy studies","volume":"81","author":"Bourges","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1097\/ICO.0000000000000699","article-title":"Transepithelial Corneal Cross-Linking With Vitamin E-Enhanced Riboflavin Solution and Abbreviated, Low-Dose UV-A: 24-Month Clinical Outcomes","volume":"35","author":"Caruso","year":"2016","journal-title":"Cornea"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ejpb.2017.01.008","article-title":"Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies","volume":"114","author":"Fathalla","year":"2017","journal-title":"Eur. J. Pharm. 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