Lipid-PLGA hybrid nanoparticles of paclitaxel: Preparation, characterization, in vitro and in vivo evaluation.

ABSTRACT

Paclitaxel loaded lipid-polymer nanoparticles (NPs) were successfully synthesized using poly lactide-co-glycolide (PLGA) as polymer and stearyl amine, soya lecithin as lipids via single step nanoprecipitation method. The study was aimed to combine the advantage of structural integrity of hybrid NPs containing PLGA core and lipid in the shell. Surfactants such as polyvinyl alcohol (PVA), tocopheryl polyethylene glycol succinate (TPGS), pluronic 68 (F68) and human serum albumin (HSA) were used as stabilizers. NPs were characterized w.r.t. morphology, particle size, zeta potential, encapsulation efficiency, in vitro drug release, protein binding capability and blood compatibility. NPs were in size range of 150-400 nm and the particle size was greatly influenced by type and concentration of surfactants and lipids. TEM analysis confirmed the spherical shape and coating of the lipid on the NPs surface. Highest percentage entrapment efficiency was observed in NPs prepared with HSA as surfactant. The release rate of paclitaxel from modified NPs was much slower as compared to unmodified NPs. The percent protein binding of P-PVA, P-TPGS, P-F68 and P-HSA (unmodified NPs) was found to be 15.11%, 16.27%, 27.90% and 33.72%, respectively demonstrating effect of surface properties of NPs on protein binding. The hemolytic activity of the NPs was found to be dependent on type of surfactant and not on the lipid employed. PVA, TPGS, F68, HSA surfactants showed ~16%, ~10%, ~13%, ~7% hemolysis rate, respectively. The surface nature of NPs had a significant effect on the circulation profile of formulations. The HSA based NPs showed prolonged blood circulation time when compared to NPs without lipid coating. Thus, the synthesized dual lipid coated PLGA NPs with HSA could act as a potential nano-system for controlled delivery of paclitaxel.