Formulation and microporation approaches for enhancing drug delivery to the anterior segment of the eye

Abstract

Ocular drug delivery remains a significant challenge due to dynamic anatomical and physiological barriers that limit drug residence time and trans-tissue permeability. Anterior segment disorders, including glaucoma, postoperative inflammation, and dry eye syndrome, typically necessitate chronic administration of topical formulations. However, conventional eye drops exhibit low bioavailability (<5%) due to rapid tear turnover, blinking, nasolacrimal drainage, and restricted corneal permeability, often resulting in poor patient adherence and suboptimal therapeutic outcomes.

This research investigates two advanced strategies to improve ocular drug bioavailability and retention: (1) self-assembling peptide-based hydrogels for anterior segment drug delivery, and (2) laser scleral microporation (LSM) combined with electrospun (ES) polymeric patches for posterior segment drug delivery. Peptide hydrogels based on L- and D-enantiomers of NAPFFKY(p) were synthesised and characterised. The D-enantiomer exhibited enhanced enzymatic resistance and prolonged release kinetics for dexamethasone and timolol maleate. Rheological profiling and cytocompatibility assays confirmed their suitability for ocular administration. Furthermore, covalent conjugation of timolol to D-peptide sequences significantly reduced initial burst release, offering controlled delivery for sustained intraocular pressure reduction.

For posterior segment access, LSM was employed to generate micropores in porcine sclera. High-resolution imaging techniques including optical coherence tomography, micro-computed tomography, scanning electron microscopy, and transmission electron microscopy elucidated micropore morphology and depth. Integration of drug-loaded ES patches with LSM-treated sclera facilitated sustained drug permeation and retention over seven days, demonstrating a promising minimally invasive transscleral delivery route. These findings underscore the potential of peptide-based biomaterials and laser-assisted permeation enhancement for developing sustained-release ocular therapies. Further in vivo investigations are warranted to evaluate pharmacokinetics, therapeutic efficacy, and long-term safety to support clinical translation.

Thesis is embargoed until 31 July 2030.

Date of Award	Jul 2025
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Commissionerate of Social Welfare, Government of Maharashtra, Pune, India
Supervisor	Thakur Raghu Raj Singh (Supervisor), Lalitkumar Vora (Assistant Supervisor) & Garry Laverty (Assistant Supervisor)