Madaan, Shivam;
(2020)
Developing Implants for Ophthalmic Drug Delivery and Flow Modulation.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Glaucoma is the leading cause of irreversible blindness worldwide. Surgical interventions are frequently necessary to lower the intraocular pressure (IOP) and do so by creating a new channel for aqueous humour to drain into the subconjunctival space. This channel can be formed by performing a glaucoma filtration surgery (GFS) or by implanting a glaucoma drainage device (GDD). However, excessive scarring at the surgical site blocks aqueous outflow, elevates IOP, and results in treatment failure. Drugs injected locally to control scarring rapidly clear from the subconjunctiva, and current implants are susceptible to a foreign body response. This work investigated strategies that could improve the outcomes of these current glaucoma interventions. First, drug-eluting spacers were formulated using established biocompatible materials to prolong drug release in conditions representing the subconjunctival space post-GFS or GDD implantation. Of these formulations, the spacer containing non-ionic surfactant, Brij 98, at a concentration of 1.25% w/v was able to prolong the release of dexamethasone from poly(2-hydroxyethyl methacrylate) pHEMA hydrogels significantly longer (>30 days) than hydrogels containing no surfactant (<7 days) at therapeutically relevant drug concentrations in vitro. Next, engineering principles were applied to inflated elastomeric membranes, which provided novel insights into considerations needed to design a novel ophthalmic drug delivery pump. Pocket geometry and material properties had a significant impact on internal pressure and subsequent pump function. Modelling data supports the feasibility of elastomeric pumps for prolonged subconjunctival drug delivery. Finally, an alternative mechanism of IOP control was investigated. Novel and established hydrogel formulations were evaluated for aqueous permeability and mechanical integrity. Despite evidence to suggest the feasibility of hydrogels to modulate aqueous flow, the in vitro permeability of hydrogel candidates was determined to be too low to maintain optimal IOP. Furthermore, hydrogel permeability tended to negate its mechanical integrity, making them unsuitable candidate materials for GDD development.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Developing Implants for Ophthalmic Drug Delivery and Flow Modulation |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/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.ucl.ac.uk/id/eprint/10117250 |
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