Cross-Linked Collagen Shields for Ocular Drug Delivery

Abstract

Background and Aim: Glaucoma is a common progressive eye disease which is estimated to affect over 60.5 million people worldwide and can result in blindness if untreated. In New Zealand, glaucoma accounts for 16% of vision loss in patients aged 50 years and over. One of the major drawbacks with conventional eye drop treatment is the low ocular bioavailability and poor patient adherence to therapies. Developing a controlled release drug delivery system would increase the therapeutic efficacy and significantly enhance patient compliance which could ultimately preserve the sight of patients suffering from glaucoma. Therefore, the main aim of this project was to develop a cross-linked collagen shield loaded with pilocarpine for efficient management of glaucoma. Methods: Various concentrations of metal oxide nanoparticles (NPs) namely zinc oxide (ZnO), PVP capped zinc oxide (ZnO/PVP) and titanium dioxide (TiO2) were first evaluated for their toxicities and were then used as cross-linking agents for the development of crosslinked collagen shields. Prepared shields were then characterised in terms of transparency, mechanical strength and bioadhesive properties. The application of UV light to enhance cross-linking was also investigated. Finally, the optimised shields were loaded with pilocarpine and the in vitro release profile was studied over a period of 14 days. Results and Discussion: Evaluation of the metal NPs showed that ZnO/PVP NPs were the least toxic and when added to collagen produced a hydrogel with the highest transparency. Therefore, ZnO/PVP NPs were selected as the most suitable cross-linking agent. A ratio of 1:1 w/w (collagen:ZnO/PVP NPs) was found to produce shields with good mechanical and bioadhesive properties. In vitro release studies of zinc showed the concentration of ions released was below the IC50 making them safe for ocular use. In vitro release studies of pilocarpine revealed that the drug could successfully be released over a period of 14 days. The application of UV irradiation to the collagen shields enhanced the cross-linking density and resulted in a slower release rate of both the zinc ions and pilocarpine. Conclusion: Collagen corneal shields cross-linked with ZnO/PVP NPs can successfully deliver pilocarpine over a prolonged duration of time compared with the conventional eye drops and seem more transparent than commercially available collagen shields. The here developed shields therefore have the potential to sustain the release of pilocarpine over prolonged periods and therefore significantly enhance patient compliance as well as therapeutic outcomes.