Optimization by design of etoposide loaded solid lipid nanoparticles for ocular delivery: Characterization, pharmacokinetic and deposition study

Abstract

The present study was to develop etoposide loaded solid lipid nanoparticles (SLN) and optimize it for effective ocular delivery to the posterior eye. SLN were prepared by melt-emulsification and ultrasonication technique. Etoposide loaded SLN were optimized by using three-factor three levels Box-Behnken design to establish the functional relationships between variables on responses of particle size, polydispersity index (PDI) and entrapment efficiency (EE). SLN were characterized for size & surface morphology, entrapment efficiency and in vitro release. Further the pharmacokinetic study of optimized formulation after intravitreal administration was evaluated in Wister rats. The deposition in the ocular tissues was checked by scintigraphic analysis in Albino rabbits. Histology was also done to evaluate morphological changes if any occur after treatment. The particle size, PDI and EE obtained for the optimized formulation (Z15) were 239.43 ± 2.35 nm, 0.261 ± 0.001 and 80.96 ± 2.21% respectively. Single intravitreal administrations of SLN were able to give sustained etoposide concentration in the vitreous for 7 consecutive days which was also supported by the results of Gamma scintigraphic study. Histology of posterior ocular tissues do not showed any serious toxic effect. Therefore it can concluded that etoposide loaded SLN was able to maintain vitreous concentration of drug without any serious toxic effect to the surrounding ocular tissues after an intravitreous administration in rat eye.