Targeting Efficacy of Simvastatin for Hormone-Dependent Carcinomas through Solid Lipid Nanoparticles

Folate conjugated Simvastatin loaded Solid lipid nanoparticles (SIM-SLNs) were constructed after the preformulation studies such as Differential calorie metry (DSC), Fourier transform infrared spectroscopy (FTIR) and partition coefficient studies. SIM-SLNs were evaluated in terms of particles size, zeta potential, drug encapsulation, and drug release. The cytotoxicity of the SLNs was evaluated on MCF-7 Human Breast Carcinoma cells (MCF-7 cells) by MTT assay. In vivo pharmacokinetic parameters and Bio-distribution were observed in Wistar rats. The particle size of SIM-SLNs (F6) was 177.4 nm with a zeta potential of -5.16 mV. The entrapment efficiency and drug loading was found to be higher in SIM-SLNs. SLN formulation released the drug in sustained manner over a period of 24 hours. Various kinetic models were fitted and it was observed that Higuchi’s model was the best fit model. SIM-SLNs showed highest cytotoxicity in tumor cells in vitro. In vivo studies showed that there is significant increase in the pharmacokinetic parameters and Bio-distribution of SIM-SLNs when compared to the pure drug suspension. Higher relative bioavailability would be due to avoidance of first-pass hepatic metabolism by intestinal lymphatic transport, which circumvents the liver. According to these results, the novel SIM-SLNs provided sustained release of the drug, and these systems are the preferred drug carriers for lipophilic drugs to overcome the oral bioavailability problem of drug and to increase targeting efficacy to the specific organs as breast, prostate and ovary.