Formulation and Evaluation of Pravastatin Sodium-Loaded PLGA Nanoparticles: In vitro-in vivo Studies Assessment

Purpose: Pravastatin sodium (PVS) is a hypolipidemic drug which suffers from extensive first-pass metabolism and short half-life. Poly(D,L-lactide-co-glycolide) (PLGA) is considered a promising carrier to improve its hypolipidemic and hepatoprotective activities.Methods: PVS-loaded PLGA nanoparticles (PVS-PLGA-NPs) were prepared by double emulsion method using a full 32 factorial design. The in vitro release and the physical stability studies of the optimized PVS-PLGA-NPs (F5) were performed. Finally, both hypolipidemic and hepatoprotective activities of the optimized F5 NPs were studied and compared to PVS solution.Results: All the studied physical parameters of the prepared NPs were found in the accepted range. The particle size (PS) ranged from 90 +/- 0.125 nm to 179.33 +/- 4.509 nm, the poly dispersity index (PDI) ranged from 0.121 +/- 0.018 to 0.158 +/- 0.014. The optimized NPs (F5) have the highest entrapment efficiency (EE%) (51.7 +/- 5%), reasonable PS (168.4 +/- 2.506 nm) as well as reasonable zeta potential (ZP) (-28.3 +/- 1.18mv). Solid-state characterization indicated that PVS is well entrapped into NPs. All NPs have distinct spherical shape with smooth surface. The prepared NPs showed a controlled release profile. F5 showed good stability at 4 +/- 2 degrees C during the whole storage period of 3 months. In vivo study and histopathological examination indicated that F5 NPs showed significant increase in PVS hypolipidemic as well as hepatoprotective activity compared to PVS solution.Conclusion: The PVS-PLGA-NPs could be considered a promising model to evade the first-pass effect and showed improvement in the hypolipidemic and hepatoprotective activities compared to PVS solution.

Automated summary

In this study, PVS-loaded PLGA nanoparticles were prepared to improve the hypolipidemic and hepatoprotective activities of PVS. The optimized nanoparticles showed suitable particle size, entrapment efficiency, and stability, and demonstrated significant hypolipidemic and hepatoprotective activities in vivo.