Amino-decorated mesoporous silica nanoparticles for controlled sofosbuvir delivery.

ABSTRACT

The present study describes synthesis of amino-decorated mesoporous silica nanoparticles (MSNs) for sustained delivery and enhanced bioavailability of sofosbuvir. Sofosbuvir is active against hepatitis C virus and pharmaceutically classified as class III drug according to biopharmaceutics classification system (BCS). MSNs were synthesized using modified sol-gel method and the surface was decorated with amino functionalization. Drug loaded MSNs were also grafted with polyvinyl alcohol in order to compare it with the amino-decorated MSNs for sustained drug release. The prepared MSNs were extensively characterized and the optimized formulation was toxicologically and pharmacokinetically evaluated. The functionalized MSNs of 196 nm size entrapped 29.13% sofosbuvir in the pores, which was also confirmed by the decrease in surface area, pore volume and pore size. The drug-loaded amino-decorated MSNs revealed an improved thermal stability as confirmed by thermal analysis. Amino-decorated MSNs exhibited Fickian diffusion controlled sofosbuvir release as compared with non-functionalized and PVA grafted MSNs. Amino-decorated MSNs were deemed safe to use in Sprague-Dawley rats after 14-days exposure as confirmed by the toxicological studies. More interestingly, we achieved a 2-fold higher bioavailability of sofosbuvir in Sprague-Dawley rats in comparison with sofosbuvir alone, and the Tmax was delayed 3-times indicating a sustained release of sofosbuvir.