Amino-decorated mesoporous silica nanoparticles for controlled sofosbuvir delivery.
Eur J Pharm Sci
; 143: 105184, 2020 Feb 15.
Article
de En
| MEDLINE
| ID: mdl-31846695
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Antiviraux
/
Propylamines
/
Silanes
/
Vecteurs de médicaments
/
Silice
/
Nanoparticules
/
Sofosbuvir
Langue:
En
Journal:
Eur J Pharm Sci
Sujet du journal:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Année:
2020
Type de document:
Article
Pays d'affiliation:
Pakistan