Development of nanoparticle-loaded microneedles for protein and hydrophobic molecules delivery to the posterior segment of the eye

Abstract

Retinal diseases caused by abnormal neovascularisation are the leading cause of irreversible blindness and pose a significant threat to patients’ quality of life and global health. However, due to the challenges of efficiently delivering drugs to the posterior segment of the eye, even though various therapeutic molecules (e.g. anti-VEGF agents and anti-inflammatory agents) have been investigated, abnormal neovascular diseases (e.g. AMD, DR and CNV) remain a global health threat. Given the chronic nature of retinal diseases and the high efficiency of intravitreal clearing, frequent injections via highly invasive conventional hypodermic needles are required to maintain therapeutic levels. However, this procedure not only causes pain and discomfort for patients but also increases the risk of harmful complications. Thus, an alternative delivery system with minimal invasiveness and the ability to sustain and control drug release is urgently desirable. As micron-scale devices, microneedles (MNs) are minimally invasive and can bypass physical barriers of the eye by generating aqueous channels, thereby achieving improved therapeutic efficacy. This thesis explores the development of dissolving MNs-based drug delivery system to promote transscleral delivery of proteins (anti-VEGF agents) and hydrophobic molecules (anti-inflammatory agents). Protein molecules and hydrophobic molecules were formulated into nanoparticles (NPs) and nanosuspensions (NS), respectively, to sustain the release of proteins and facilitate the incorporation of hydrophobic molecules into the polymeric matrix, thereby forming the hybrid system of dissolving MNs and NPs/NS. It was revealed that the optimised NPs/NS-loaded MNs are strong and sharp enough to penetrate the sclera and provide rapid dissolution after insertion without causing irritation. This thesis provides considerable evidence to support the use of dissolving MNs as minimally invasive and therapeutic effective intraocular delivery platforms for retinal disease therapy.

Date of Award	Jul 2022
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Thakur Raghu Raj Singh (Supervisor) & Krishnagoud Manda (Supervisor)