Engineered bio-adhesive polyhedral oligomeric silsesquioxane hybrid nanoformulation of amphotericin B for prolonged therapy of fungal keratitis

Abstract Even though fungal keratitis is a severe corneal disease that can lead to permanent vision loss, its therapeutic management is still problematic. This limitation is in part attributable to the fact that tear film renewal curtails exposure time of drug containing eye drops to the ocular surface. Accordingly, anti-microbial therapy needs to be performed repeatedly. Efforts to resolve this hindrance include developing formulations that prolong drug retention on the ocular surface which can in turn improve therapeutic efficacy as well as reduce administration frequency. To extend drug residence time on the ocular surface, we designed a novel organic-inorganic hybrid consisting of a PEG-PPG copolymer modified with polyhedral oligomeric silsesquioxane (POSS) groups. Its tailored POSS-micelles possess both good biocompatibility and bio-adhesiveness, which improve ocular delivery of poorly soluble drugs. We describe here use of a novel mouse fungal keratitis model to determine the effects of this formulation encapsulating amphotericin B (AMB) on this condition. The results show that POSS-micelles significantly prolonged AMB retention time on the ocular surface, leading to improved resolution of this disease. Moreover, this treatment strategy had no toxic effects during ocular administration either in vitro or in vivo. Therefore, this POSS formulation bearing AMB has the potential to prolong drug retention time and improve its therapeutic efficacy in managing fungal keratitis.