Natamycin Ocular Delivery: Challenges and Advancements in Ocular Therapeutics

Abstract

Fungal keratitis, an ocular fungal infection, is one of the leading causes of monocular blindness. Natamycin has long been considered the mainstay drug used for treating fungal keratitis and is the only US Food and Drug Administration (USFDA)-approved drug, commercially available as a topical 5% w/v suspension. Furthermore, ocular fungal infection treatment takes a few weeks to months to recover, and the available marketed antifungal suspensions are associated with poor residence time, limited bioavailability (< 5%) and high dosing frequency as well as minor irritation and discomfort. Despite these challenges, natamycin is still the preferred drug choice for treating fungal keratitis, as it has fewer side effects and less ocular toxicity and is more effective against Fusarium species than other antifungal agents. Several novel therapeutic approaches for the topical delivery of natamycin have been reported to overcome the challenges posed by the conventional dosage forms and to improve ocular bioavailability for the efficient management of fungal keratitis. Current progress in the delivery systems uses approaches aimed at improving the corneal residence time, bioavailability and antifungal potency, thereby reducing the dose and dosing frequency of natamycin. In this review, we discuss the various strategies explored to overcome the challenges present in ocular drug delivery of natamycin and improve its bioavailability for ocular therapeutics.

Fungal Keratitis, Epidemiology and Outcomes in a Tropical Australian Setting

“…Natamycin exhibits broad-spectrum activity and is particularly effective against Fusarium spp., a common cause of fungal keratitis, as well as Aspergillus spp. [ 14 ]. Natamycin is typically administered topically as eye drops or ointment and is generally well-tolerated with minimal systemic absorption.…”

“…Antifungal susceptibility testing could provide valuable information on the susceptibility of fungal isolates to natamycin and help to guide treatment decisions, particularly in cases of refractory or recurrent fungal keratitis. However, MIC results should be interpreted in conjunction with clinical data and other factors, such as corneal penetration of the antifungal agent and patient response to therapy, to optimise treatment outcomes [ 14 ]. Additionally, natamycin MIC testing was not available over the course of this study.…”

Breaking Down the Barriers of Drug Resistance and Corneal Permeability with Chitosan-Poly(ethylene glycol)-LK13 Peptide Conjugate to Combat Fungal Keratitis

“…NAT exhibits stronger antifungal activity, lesser side effects, and lower resistance rates compared to other antifungals, which support its treatment efficiency in FK, especially in superficial FK. 7,8 Nevertheless, previous reports demonstrated that only 7.6% of FK patients could be resolved by topical antifungals. 9 On the one hand, drug-resistant fungal infections are emerging as an important clinical problem.…”