Development of thermosensitive in situ gel nanoemulsions for ocular delivery of acyclovir

Abstract

The aim of the current study was to formulate thermosensitive in situ gel nanoemulsions (NEs) containing acyclovir (ACV) for ocular drug delivery and evaluate their ex vivo corneal permeation ability and ocular irritation possibility. ACV loaded NEs were prepared by low energy method. Physicochemical properties, drug release, and stability studies of in situ gel NEs were investigated. The optimized formulation was chosen for excised bovine corneal permeation, hen's egg test-chorioallantoic membrane and modified Draize tests to evaluate its ocular permeation and irritation. The optimum in situ gel NE consisting Triacetin, Transcutol®P, Poloxamer 407, and Poloxamer188 had the mean droplet size and polydispersity index of 28 nm and 0.38 respectively. Moreover, physicochemical properties such as pH, viscosity, osmolality, and refractive index were acceptable for ocular administration. This formulation showed a sustained drug release pattern compared to the control solution. Based on the permeation study results, drug permeation of optimum formulation was about 2.8-fold higher than the control solution. Irritation tests illustrated that the optimum in situ gel NE could be well tolerated by the eye. In conclusion, these results demonstrated that this new ACV formulation could be considered as a novel ophthalmic delivery system for the treatment of ocular viral infections.