Acyclovir Loaded Solid Lipid Nanoparticulate Gel for Ocular Delivery: Optimization by using Factorial Design

Abstract

Background: Acyclovir is a potent antiviral agent primarily used to treat viral infection in the eye, signified as Herpes Simplex Keratitis caused by Herpes Simplex Virus-1. But its applications are limited because of its poor oral bioavailability and permeability caused by significant first-pass metabolism. Objectives: The study is to design the formulation, optimization, in-vitro, ex-vivo and in-vivo characterization of solid lipid nanoparticulate gel (SLNG) of acyclovir and inspect their possibility in ocular applications. Methods: SLNG of acyclovir was prepared by hot homogenization technique and optimized by 2 3 factorial design and evaluated for in-vitro physicochemical characteristics and in-vivo pharmacokinetic study. Response surface methodology estimations and plots for optimization to obtain optimum values for response variables based on desirability criteria was performed using Design-Expert software. Results: The optimized formulation showed a particle size of 193.57±1.14 nm, zeta potential of 35±1.98 mv, drug entrapment efficiency of 82±1.59% and drug loading efficiency of 54.10±0.79%, indicating good physical stability. The transcorneal study showed a significant increase in drug permeation across the cornea as compared with the control. The drug release kinetics of the prepared formulations was best fitted to the first-order kinetic model. In-vivo pharmacokinetic studies revealed a significant enhancement in the drug level in the blood plasma of the optimized formulation as compared to the pure drug suspension. Conclusion: The acyclovir-loaded SLN gel was successfully developed, optimized, evaluated and exhibited enhanced drug permeation as well as systemic bioavailability through excised corneas. Thus, SLNG acts as a favorable approach for ocular applications of acyclovir.