Intranasal optimized solid lipid nanoparticles loaded in situ gel for enhancing trans-mucosal delivery of simvastatin

摘要

The aim of this study was to develop optimized simvastatin (SMV) solid lipid nanoparticles (SLNs) with subsequent loading into a thermosensitive in situ gel (ISG) to enhance and control intranasal drug permeation. Three formulation factors were optimized for their effect on particle size and entrapment efficiency (EE). SLNs components were studied thru solid-state characterization. The optimized formulation was morphologically characterized and loaded into poloxamer ISG formulations of different concentrations. Evaluations were done for gelation temperature, viscosity, muco-adhesion strength, and in vitro and ex vivo permeations. Transport across nasal mucosal layers was characterized using a fluorescence laser microscope. The studied factors significantly affected particle size and EE. The drug was successfully encapsulated and homogenously dispersed in the lipid matrix and changed from a crystalline to amorphous state in the optimized SLNs. Transmission electron microscope illustrated the presence of nanoparticles, while scanning electron microscope observations indicated fusion of the particles. An ISG formulation containing 22% poloxamer loaded with optimized SLNs exhibited better mucoadhesion and ex vivo drug permeation, and was able to penetrate deeper into the nasal tissue when compared to the same formulation loaded with pure drug. No signs of inflammation or necrosis were observed upon histopathological study. In summary, this thermosensitive ISG formulation containing SMV SLNs can be considered as an alternative to currently available oral drug formulations, however, further pre/clinical studies are needed.