The multifunctional synergistic effect of chitosan on simvastatin loaded nanoparticulate drug delivery system

The present study reported design and evaluation of nanoformulations of Simvastatin using different polymers. The study emphasizes upon the synergistic activity of the drug and the polymers owing to the reported anti- hyperlipidemic activity of the selected polymers. Preliminary studies advocated for chitosan formulations due to the expected particle size (543 ± 26 nm) among the three polymer formulations. Four formulations (F1-F4) were prepared varying chitosan ratio. F4 demonstrated optimal characteristics (particle size − 549 ± 23.43 nm, narrow size distribution − 0.515 ± 0.06) and qualified for further investigation. The formulation parameters modified the intrinsic properties of chitosan. Formation of low M. wt chitosan (70,000 ± 10,000 Da) enhanced swelling & mucoadhesive properties. These influenced the drug properties in which amorphization of drug increased solubility and decreased partition coefficient. This led to better absorption at intestine sustaining the drug release up to 66.18 ± 1.26% in SIF during the in vitro study. Better absorption was confirmed by reduction in lipid profile with several fold reduced dose in mouse model. The in vitro bile binding property of chitosan in formulation demonstrated the enhancement of hypolipidemic activity of Simvastatin. The outcomes of the study showed a successful preparation of optimum nanoformulations and also revealed possible synergistic functionalities of chitosan and the Simvastatin as potential hypolipidaemic modality without any toxic manifestations.