Strategies to Improve Ocular Bioavailability and Biodistribution of Low Molecular Weight Therapeutics and Biopharmaceuticals

Diplôme Thèse Strategies to Improve Ocular Bioavailability and Biodistribution of Low Molecular Weight Therapeutics and Biopharmaceuticals eng 2022-09-13 2022-10-05 author Gonzalez Iglesias Laura Gisela 0000-0003-2371-4228 850985 director Kalia Yogeshvar 0000-0001-9049-5489 503798 259 10.13097/archive-ouverte/unige:167551 urn:nbn:ch:unige-1675517 Sc. Vie - Pharma. 188 The aim of this project was to explore novel strategies to optimize the delivery of low and high-molecular-weight drugs in the anterior and posterior segments of the eye such as the use of nanoformulations, chemical modification of drug properties and physical enhancement strategies to improve the treatment of ocular diseases. Chapter I presents a literature review on the fascinating anatomy of the eye, the different routes of ocular administration of drugs and the challenges and strategies to reach the anterior and posterior segments are presented. Chapters II and III present different strategies to improve the treatment of fungal keratitis. Chapter II describes the formulation of triple antifungal nanosystems (micelles and liposomes) containing Natamycin (NAT), voriconazole (VOR) and caspofungin acetate (CAS) to assess their potential for simultaneous drug delivery into the cornea and anterior segment of the eye. In Chapter III a second approach to improve the treatment of fungal keratitis was explored with the use of iontophoresis to increase CAS delivery to the anterior and posterior portions of the eye. Chapter IV explores the use of the prodrug approach to obtain aciclovir derivatives with suitable characteristics (charge and high aqueous solubility) to be transported across ocular membranes by iontophoresis. Finally, the results obtained in Chapter V demonstrate that the use of iontophoresis is not limited to small molecules, as it was shown that the transscleral delivery of a small protein - Cyt c - can be modulated by modifying the iontophoretic conditions. The different strategies presented in this work are promising options to improve the treatment of ophthalmic diseases. Eye Ocular delivery Iontophoresis Transcorneal Transscleral Micelles Liposomes Prodrug Natamycin Voriconazole Caspofungin acetate Cytochrome c Dewey 615 31 Section des sciences pharmaceutiques 17 false 39a2d74d-3ffb-4b83-a687-723cafed2f34 Thesis Restricted Thesis manuscript_Laura G_Gonzalez_.pdf 11334219 application/pdf Private 2023-10-05 bd9bc21a0def63351c81fd5c68c2ac65ff42311c67e7f14cd6d1a9f5fcf5d813 de0dd4d7-2b08-4ba4-bc4b-74fd966adb3f Imprimatur Public imprimatur.pdf 742617 application/pdf 6c5ff586580d5fc8a04500d2f7b831419729777f67c00d97708034b562212d2f restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

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Strategies to Improve Ocular Bioavailability and Biodistribution of Low Molecular Weight Therapeutics and Biopharmaceuticals				2022	445	9

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Gonzalez Iglesias, Laura Gisela

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