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Doxycycline-Loaded Biodegradable Microparticles as a Novel, Safe, Anti-Scarring Strategy in the Eye

Alberini, Fiorella; (2023) Doxycycline-Loaded Biodegradable Microparticles as a Novel, Safe, Anti-Scarring Strategy in the Eye. Masters thesis (M.Phil), UCL (University College London). Green open access

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Abstract

The consequences of untreated trachoma induced trichiasis and glaucoma depend on the success of their surgical treatments, which can fail due to the rise in post-operative scarring. Symptomatology reset of both conditions is leads to blindness. Doxycycline possesses anti-scarring properties. Nevertheless, its oral administration is ineffective, thus, requiring a vehicle for targeted and progressive release at the incision site. Poly-Lactic-Glycolic-Acid (PLGA) microparticles can effectively encapsulate drugs and release them over time. This study investigated the effects of doxycycline-loaded particles (doxPLGA) and doxycycline by using standard collagens gels and a laboratory developed biomimetic model, which effectively mimics the interface in the eye where post- surgical scarring occurs. It also aimed to build on existing knowledge on the physical characterisation of doxPLGA. It hypothesised that the particles would be more effective at preventing contraction than high concentrations of doxycycline. The study corroborated that the efficacy of doxPLGA particles is dependent on the release of doxycycline from PLGA and showed that their effects are at least comparable to doxycycline in medium at preventing the contraction of the biomimetic model. Importantly, the study also revealed that doxycycline induces an apparent cell death on ocular fibroblasts in RPMI medium that is not rescued in the presence of serum. In contrast, in DMEM medium, doxycycline generally caused a significant decrease in gel contraction. Doxycycline also caused a reduction in cell number within the bilayer gels and biomimetic model in complete DMEM medium, which was not apparently due to cytotoxicity. Regarding the physical characterisation studies, it was seen that subjecting the particles to dynamic flow conditions or in the absence of a coating hydrogel accelerates doxycycline release with respect to static coated conditions. Lastly, under static conditions, doxycycline release was not accelerated by the presence of a higher number of closely surrounding cells. Altogether, the data suggests that doxPLGA holds potential to become an effective treatment for ocular post-surgical scarring.

Type: Thesis (Masters)
Qualification: M.Phil
Title: Doxycycline-Loaded Biodegradable Microparticles as a Novel, Safe, Anti-Scarring Strategy in the Eye
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10180208
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