Fitaihi, Rawan A;
(2023)
Design and Development of Particle-Loaded Ocular Microneedle Arrays Prepared Using 3D Printing.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Microneedle-based systems have emerged as a minimally invasive method to enhance drug delivery. While this approach has been primarily designed for transdermal uses, new applications of microneedles (MN) have recently been developed, including the delivery and localisation of therapeutic agents within ocular tissue. Ocular diseases may represent a significant challenge for drug delivery, as penetration of drugs into the ocular tissues is a major limiting factor in the treatment of vitreoretinal diseases. In this PhD project, a novel ocular drug delivery system was developed by formulating a dissolvable MN array loaded with biodegradable polylactic-glycolic acid (PLGA) particles for scleral drug deposition. Moulds with a range of geometric features were prepared using a stereolithography 3D printer. The optimised moulds were used to prepare PVP/PVA dissolvable MN arrays loaded with PLGA particles. The mechanical strength and the insertion force were tested ex-vivo on porcine scleral tissue. The MN array was strong enough to penetrate scleral tissue and subsequently dissolve within the tissue. Dexamethasone was selected in this study as a model drug to be loaded into the PLGA particles. The permeation through scleral tissue was tested; the MN arrays showed a significantly higher permeation than topically administered dexamethasone suspension. Additionally, more than 10% of the dexamethasone in the MN array was detected in the vitreous humour of excised porcine eye one hour post application. The effect of size and surface charge on the particle’s distribution diffusion in the sclera was assessed by applying fluorescent labelled micro- and nano- particles and PLGA particles. All particle types were found to diffuse within the scleral tissue. Thus, this platform can be potentially tailored to prepare a minimally invasive drug delivery system for a wide range of therapeutics. In-vivo studies have also been performed to evaluate ocular irritancy and assess the behaviour of the systems in endotoxin-induced 4 uveitis rabbit model. The in-vivo study demonstrated that the system has minimal irritation to rabbit eyes and could serve as a safe and effective drug delivery platform.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Design and Development of Particle-Loaded Ocular Microneedle Arrays Prepared Using 3D Printing |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10168206 |
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