Development and Optimization of Lipid-polymer Hybrid Nanoparticles Containing Melphalan Using Central Composite Design and Its Effect on Ovarian Cancer Cell Lines

The development of controlled-release drug delivery systems has a great potential to improve the efficacy of anticancer drugs. This study aimed to develop and optimize the production of hybrid lipid-polymer nanoparticles (HLPNPs) for the targeted delivery of melphalan anticancer drugs. Response surface methodology (RSM) and central composite design (CCD) were used to evaluate and optimize the effects of three independent variables including lipid, polymer, and polyvinyl alcohol (PVA) ratios on the nanoparticles (NPs) size and drug entrapment efficiency (EE%). Hybrid NPs were prepared using the nanoprecipitation method. The results demonstrated that spherical NPs were synthesized, and the rate of EE% went up by increasing the polymer as well as decreasing the PVA concentrations. The nanoformulation released melphalan in a sustained and controlled manner (17.39% in a period time of 48 h). Also, cytotoxicity evaluations showed that HLPNPs caused an increase in the efficacy of melphalan against human ovarian A2780CP and SKOV3 cancer cells. Overall, the results of this study demonstrated that HLPNPs can be considered as a promising carrier for the delivery of hydrophobic anticancer drugs such as melphalan and the evaluation in-vivo.