Development and Characterisation of Novel Nanoparticle-Loaded Contact Lenses for the Treatment of Posterior Segment Diseases of the Eye

Chau Thuy Nguyen, Dan (2023) Development and Characterisation of Novel Nanoparticle-Loaded Contact Lenses for the Treatment of Posterior Segment Diseases of the Eye. Doctoral thesis, SETU Waterford.

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Abstract

Treatment of ocular diseases face challenges such as low drug bioavailability from topical routes and side effects from intravitreal injection (e.g., retinal detachment and infection). The sophisticated ocular anatomy, while protecting the eye, also prevents therapeutic compound from readily reaching the target site. This project aims to address these challenges through the development of a hydrogel soft contact lens (SCL) impregnated with drug:cyclodextrin complex-loaded biodegradable and biocompatible polymeric nanoparticles (NPs) designed for controlled release and enhanced corneal permeation. Daily disposable hydrogel SCLs (nesofilcon A materials) were successfully fabricated at an academic research lab utilising a comparable process to an industrial commercialized lens manufacturing approach. Naringenin (NAR) was chosen as the drug in this study because of its antioxidant and anti-inflammatory activities as an ocular therapeutic. NAR-loaded SCLs exhibited comparable critical lens parameters with >98% optical transparency, >75% water content, a lens diameter of 14.10-14.20 mm and a Young’s modulus of 0.51-0.55 MPa. A controlled daily drug delivery was achieved within the estimated therapeutic range of 17.88 – 54.42 μg NAR/day. In order to improve ocular bioavailability and permeation of NAR, a NAR:SBE-ß-CD (sulfobutyl ether-β-cyclodextrin) inclusion complex was formed using a freeze-drying monophasic system approach. A notable increase (6480-fold) in NAR aqueous solubility was obtained arising from complexation. In addition, this complex was used in the synthesis of a NAR-loaded chitosan (CS) NP through an ionic gelation process (333.3 ± 26.6 nm, +22.0 ± 4.3 mV, and a PDI of 0.0777 ± 0.0580). NAR-loaded CS NPs had a %encapsulation efficiency of 37.4 ± 4.0%, while providing a sustained drug release for 30 days through a diffusion-controlled mechanism. These two drug carrier systems were subsequently loaded into the developed SCLs. Based on the characterized physicochemical properties of the loaded SCLs, a ‘soak and release’ approach was determined to be the optimum method. The release mechanism of NAR in complex- and NP-loaded SCLs was governed by both diffusion and swelling, with a drug release rate of 45.95 ± 2.06 and 45.96 ± 5.18 μg NAR/day, respectively. The results from this research demonstrated that the developed models could act as promising drug delivery systems to provide a more sustained, less invasive, and controlled delivery of a drug or supplement to the eye. Outcomes from this work suggest potential areas for future work that can lead to the commercialization of the studied technologies.

Item Type:	Thesis (Doctoral)
Uncontrolled Keywords:	Novel Nanoparticle-Loaded Contact Lenses, Posterior Segment Disease
Departments or Groups:	Pharmaceutical and Molecular Biotechnology Research Centre
Divisions:	School of Science > Department of Chemical and Life Sciences
Depositing User:	Derek Langford
Date Deposited:	09 Oct 2023 13:27
Last Modified:	09 Oct 2023 13:27
URI:	https://repository.wit.ie/id/eprint/7749

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