Long circulating chitosan/PEG blended PLGA nanoparticle for tumor drug delivery.

Polymeric nanoparticles have long been sought after as carriers for systemic and targeted drug delivery. The ability of these particles to circulate in the bloodstream for a prolonged period of time is often a prerequisite for successful targeted delivery. To achieve this, paclitaxel loaded chitosan and polyethylene glycol coated PLGA (PLGA-CS-PEG) nanoparticles were formulated and characterized that could efficiently encapsulate hydrophobic drugs, and also evade the phagocytic uptake by reducing opsonization by blood proteins, hence increasing the bioavailability of the drug. In our study, we primarily assessed a rational approach for designing and formulating ideal long-circulating nanoparticles by optimizing the concentration of chitosan (CS) and polyethylene glycol (PEG). Uptake efficiency and in vitro cytotoxicity of the formulated nanoparticles was also evaluated in different cancer cell lines (retinoblastoma, breast cancer and pancreatic cancer). PLGA-CS-PEG nanoparticles showed dramatic prolongation in blood circulation, as well as reduced macrophage uptake, with only a small amount of the nanoparticles sequestered in the liver, when compared to PLGA-CS and PLGA nanoparticles. Superior anti-proliferative effect and cell cycle inhibition was observed in case of PLGA-CS nanoparticles and PLGA-CS-PEG nanoparticles over PLGA nanoparticles and native paclitaxel, which may be due to higher cellular uptake resulting in greater antiproliferative activity of nanoparticles. The present results thus suggest that, a combinational coating of PEG and chitosan may represent a significant step in the development of long-circulating drug delivery carriers for tumor drug delivery. Copyright