DEVELOPMENT AND EVALUATION OF VALACYCLOVIR-LOADED POLYMERIC NANOPARTICLES FOR ENHANCED OCULAR DRUG DELIVERY

Abstract

For ocular herpes, valacyclovir, a prodrug of acyclovir, is the recommended medication. However, inadequate corneal permeability, fast precorneal loss, and low ocular bioavailability restrict its therapeutic effectiveness. The study was aimed at coming up with and then investigating chitosan-based nanoparticulate system for delivery of valacyclovir into the eye across the barriers to enhance drug retention and penetration at site of infection. Chitosan nanoparticles were prepared with the framework of 2D model, using ionic gelation method through STPP as cross-linker loaded with valacyclovir. The properties that were tested for nanoparticles: Size of the particles; Zeta potential; Morphology; Entrapment Efficiency of drug; In vitro drug release. The enhanced composition (F-9) revealed a high encapsulation efficiency of 83.6±1.4 per cent, +28.4 mV as the zeta potential and particle size of 185.2±2.1 nm. FTIR and DSC experiments confirmed that the drug did not show any major chemical interaction with the polymer. Smooth, spherical particles of uniform distribution were seen in scanning electron microscopy. In vitro drug release studies which followed Higuchi kinetic model was evidence of sustained release of valacyclovir from the nanoparticles for period of 24 hours. Further, the preparation possessed desirable physicochemical properties such as pH suitability, proper viscosity, and sterility suitable for ocular use. Studies in vivo in rabbits revealed prolonged retention and improved ocular bioavailability when compared with the marketed formulation. The reported findings show the promise that chitosan-based nanoparticles represent the vehicle of ocular delivery of valacyclovir that has a potential administration route at the lower frequency and increased therapeutic efficiency in the treatment of herpes simplex infections of the eye.