Development of a new polymer ocular insert to treat fungal infections threatening the cornea

Fungal keratitis is a kind of dangerous, sight-threatening corneal infections which crucially affects the quality of patients’ life, especially in developing countries where it is more prevalent. The infection often has more unfavorable outcomes than other types of eye infections, yet there is not much evidence to present treatment. Currently used methods of treatment applied in ophthalmology are the topical application of a drug in the form of eye drops, liquids, and emulsions. However, the anatomical and physiological structure of the eye restricts the delivery of a therapeutically active drug concentration for ocular disease treatment. Natural barriers protect the eye from different damaging factors while limiting the penetration of a drug. Consequently, such topical delivery requires increased employment in order to maintain adequate bioavailability and concentration levels. Eventually, it leads to a long-time expensive treatment. Another route is a systemic treatment, which is more effective in comparison with the topical route but limited due to a significant number of side effects. Thus, it has directed our concerns to develop a new cost-effective drug delivery vehicle, which can provide sustained and prolonged drug release. Over the past decades, the variety of ophthalmological strategies was applied with an attempt to overcome those ocular obstacles and achieve therapeutically most effective transport of the drug to targeted segments of the eye with different drugs used, namely, natamycin, econazole, voriconazole, and ketoconazole. In this study, using voriconazole as a non-toxic antifungal agent, the new polymerbased drug delivery device was developed, characterized, and in-vitro, in-vivo tested. The system is present in the form of flexible hydrogel rods with a porous structure which are loaded with the drug. This thesis work demonstrates that a polymer ocular insert can significantly reduce the dosing frequency of voriconazole administration and improve long-term patient compliance. The obtained data shows the prolonged release of drugs from the device with a peak concentration of 1.2 mg/mL within the first hour