Design and development of precisely engineered long-acting drug delivery systems to the eye

Abstract

Ocular diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy, and diabetic macular oedema are major causes of blindness worldwide. Treatment of ocular diseases through topical, systemic, and periocular routes is hindered by ocular barriers, resulting in low bioavailability. Sustained drug delivery systems, like implants, can improve therapy outcomes, reduce administration frequency, and enhance patient compliance. 3D printing technology offers the creation of personalised medicine and complex dosage forms. It has been widely used in fabricating oral dosage forms and sustained-release implants. So far, 3D printing technology has not been extensively used in manufacturing ocular drug-delivery systems. This project explores the feasibility of 3D printing technology for fabricating sustained-release ocular implants. Drugs that are known to have efficacy and safety for ocular treatment, including timolol maleate (TM), triamcinolone acetonide (TA), and axitinib (AX), were used in this study. The implants were fabricated by employing FDA-approved biodegradable polymers known to be safe for ocular applications. An appropriate analytical method based on liquid chromatography was developed and validated to quantify each drug in the implant. The safety of fabricated implants was evaluated by cell viability studies. ARPE-19 cells, representing retina cells, were used to evaluate the biocompatibility of TA-loaded and AX-loaded implants. Meanwhile, fibroblast cells, representing scleral tissue, were used to evaluate the safety of TM-loaded implants. In summary, 3D printing technology has successfully been used to fabricate small-sized sustained-release ocular implants. All implants were easy to fabricate and showed good biocompatibility. Fabricated implants can be potential candidates for overcoming the current problem of conventional ocular treatment. Nevertheless, the development of these sustained-release ocular implants is still in the early stages. Further research on the sterilisation method, scale-up, tailored degradation, and in vivo study needs to be performed to ensure efficacy, safety, and quality before clinical use.

Thesis embargoed until 31 December 2029.

Date of Award	Dec 2024
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Indonesia Endowment Fund for Education (Lembaga Pengelola Dana Pendidikan/LPDP)
Supervisor	Thakur Raghu Raj Singh (Supervisor), Lalitkumar Vora (Supervisor) & Dimitrios Lamprou (Supervisor)