Simvastatin nanolipid carriers decreased hypercholesterolemia induced cholesterol inclusion and phosphatidylserine exposure on human erythrocytes

Abstract

This study aimed to develop simvastatin (SV) loaded lipid nanocarriers as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and lipid nanoemulsion (LNE) and to estimate their in vitro erythrocyte uptake to reduce the cholesterol level. Therefore, numerous SLNs were prepared using Imwitor 900K, Stearic acid, Softisan 154 and Dynasan 118. For NLC, 30% w/v of Miglyol 812 was added to the previous lipids and LNE consisting 100% w/v of Miglyol 812 was also prepared for comparison. These lipid nanocarriers exhibited spherical-shapes with negative charges and particle size lower than 400nm (PDI<0.3). Moreover, the optimized formulations were LNE (Miglyol 812), NLC (Stearic acid and Miglyol 812) and SLN (Stearic acid), which showed the highest entrapment efficiency and drug release. In addition, the percent of erythrocyte uptake of SV from free SV solution, optimized SLN, NLC and LNE was 28%, 78%, 85% and 72%, respectively. Furthermore, incubation of erythrocytes with cholesterol enriched plasma resulted in a significant increase in the percent of cholesterol inclusion, hemolysis and eryptosis compared to control. In contrast, the incubation of erythrocytes with cholesterol rich plasma in the presence of the optimized nanocarriers resulted in a significant decrease percent of cholesterol inclusion, hemolysis and eryptosis. However, effect of the lipid nanocarriers on the measured parameters was more pronounced than that of the free drug. Thus, these results suggested that the lipid nanocarriers might be a promising nanocarrier for SV to maintain the native erythrocyte function in hypercholesterolemia.