Simvastatin-Loaded PEGylated Solid Lipid Nanoparticles: Lipid Functionalization to Improve Blood Circulation

Abstract

The aim of the present work was to formulate simvastatin-loaded PEGylated solid lipid nanoparticles (PEG-SLNs) for prolonging blood circulation. Plain solid lipid nanoparticles (P-SLNs) were prepared by ethanol injection method. Prepared P-SLNs were PEGylated using carbodiimide chemistry by coupling the amine group of bis-amine PEG with the carboxyl group of the phosphatidylcholine present on the surface of previously formed drug-loaded P-SLNs in the presence of 1-ethyl-3(3-dimethylaminopropyl) carbodiimide (EDC). The success of the pegylation of P-SLNs was confirmed by the IR spectra of P-SLNs and PEG-SLNs. The average particle size and zeta potential for P-SLNs and PEG-SLNs were found to be 322.3 ± 3.71 nm; − 32.7 ± 0.15 and 351.6 ± 1.23 nm; − 10.6 ± 0.79, respectively. DSC curves and XRD pattern confirmed the homogenous dispersion of simvastatin and concluding the presence of simvastatin in an amorphous state in both nanoparticle formulations. A biphasic in vitro drug release pattern was found with both the nanoparticles formulations, P-SLNs shows a drug release of 96.02 ± 2.41% within 48 h, while 91.89 ± 1.72% drug was released from PEG-SLNs within 72 h. PEG-SLNs were found to be less hemolytic toxic as compared to P-SLNs. Prepared PEG-SLNs were found to be long-circulating, with low elimination and better serum profiles.