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

Abstract

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°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.

Keywords:

• pravastatin sodium
• PLGA
• nanoparticles
• hypolipidemic and hepatoprotective activity

Acknowledgments

The authors would like to express their gratitude to Dr Walaa Awadin, Associate Professor, Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, for her technical support and specimen examination during the histopathological examination. The authors would like to thank Delta Pharm Pharmaceutical Co, Cairo, Egypt, and Purac Biomedical, Holland, for kindly supplying pravastatin sodium and poly(lactic-glycolic acid), respectively.

Disclosure

The authors report no conflicts of interest in this work.