Development and optimization of Riluzole-loaded biodegradable nanoparticles incorporated in a mucoadhesive in situ gel for the posterior eye segment

Abstract

Riluzole-loaded PLGA nanoparticles (RLZ-NPs) were developed to improve the biopharmaceutical profile of RLZ after ocular administration. Moreover, RLZ-NPs were dispersed in an in situ gelling system (RLZ-NPs-Gel) for topical administration as a potential neuroprotective strategy against glaucoma. Formulations were optimized using the design of experiments approach. Characterization of the physicochemical and rheological properties, as well as interaction studies were carried out. To ensure RLZ-NPs-Gel ocular safety, the irritant potential was also evaluated in vitro and in vivo. Moreover, in vivo ocular biodistribution was also undertaken. Optimized RLZ-NPs showed an average size below 200 nm, an encapsulation efficiency greater than 90% and a negative surface charge. Interaction studies of RLZ-NPs showed that RLZ was dispersed in the polymeric matrix. RLZ-NPs-Gel possess a pseudoplastic behavior and a medium-low post-gelling viscosity to avoid discomfort after ocular application. Simultaneously, RLZ-NPs-Gel were able to increase RLZ-NPs contact with the ocular surface. Both formulations demonstrated the ability to be distributed in the posterior eye segment after 24 h of their application obtaining a more delayed distribution for RLZ-NPs-Gel. Therefore, a novel in situ gelling system able to disperse RLZ-NPs has been successfully developed as innovative neuroprotective strategy for potential topical treatment of glaucoma.