期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 143, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejps.2019.105184
关键词
Functionalization; Mesoporous silica nanoparticles; Sofosbuvir; Toxicology; Surface area; Pharmacokinetics
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 T-max was delayed 3-times indicating a sustained release of sofosbuvir.
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