Development, Optimization and In vitro Evaluation of Etoposide loaded Lipid Polymer Hybrid Nanoparticles for controlled Drug Delivery on Lung Cancer

Lipid polymer hybrid nanoparticles [LPHNPs] are a system of nanoparticles which are a mixture of lipid monolayer shell and biodegradable polymer core developed for intelligent drug delivery of anti-cancer drugs. The present study aimed to develop and optimize LPHNPs for targeted delivery of etoposide anticancer drug through designing an experiment with Response Surface Methodology [RSM] and Central Composite Design [CCD] with quantitative control of three independent variables of lipid, polymer and polyvinyl alcohol [PVA] percentage which examined their effect on nanoparticle size and encapsulation efficiency [EE]. LPHNPs were prepared by one-step nanoprecipitation method. The results showed the optimizing of the tested values ​​of polymer, lipid and %PVA. Lipid-polymer hybrid formulation was reported to be about 14% after 80 hr. The cytotoxicity effect of etoposide-containing LPHNPs for lung cancer cell lines A-549 and Calu6 showed higher antitumor activity compared with the free drug used. Further, the results showed that the high polymer concentration led to more space for drug enclosure and created a relatively compact matrix; therefore, the drug encapsulation efficiency increased as the amount of polymer increased. In LPHNPs, increasing the amount of polymer, lipid and increasing the percentage of PVA used in nanocarrier synthesis generally improved particle size and encapsulation efficiency. The results also showed that LPHNPs could be effective for the delivery of hydrophobic drugs such as etoposide.

Keywords:

HLPNPs , Etoposide , Central composite design , Nanoprecipitation , MTT assay