Therapeutic Effects of Paclitaxel Loaded Polyethylene Glycol-Polylactic Acid-Glycolic Acid Copolymer Nanoparticles on Pancreatic Cancer in Rats.

Abstract

To establish a simple and safe method for the preparation of paclitaxel PEG-PLGA nanoparticles emulsified in tpgs (PTX-pegpllga-np), for high drug loading; and to study its effect on proliferation and apoptosis of human pancreatic cancer cell line MIAPACA-2. PTX-PEG-PLGA-NP was prepared by one-step precipitation, using tpgs as emulsifier. The drug loading and particle size were used as an index to optimize the formulation, and the physical and chemical properties such as in vitro release and stability were characterized. The uptake of fluorescein coumarin 6 (C6) loaded PEG-PLGA-NP by MIAPACA-2 cells was observed by fluorescence microscope, and the growth and apoptosis of MIAPACA-2 cells after PTX-PEG-PLGA-NP were detected by MTT and flow cytometry respectively. The entrapment efficiency of the nanoparticles was 90.26%, the drug loading was 10.13%, the average particle size was 92.3±3.1 nm, and the zeta potential was 10.48±1.54 mV. The cumulative releases of nano preparation and general preparation (Taxol injection) in four hours were 25.9% and 98.5%, respectively; and the former had a strong sustained-release effect. The results of cell uptake experiments showed that the uptake of c6-PEG-PLGA-NP by MIAPACA-2 cells increased gradually with time. MTT results showed that PTX-PEG-PLGA-NP had no significant difference in the inhibition rate of MIAPACA-2 cells compared with PTX group. Flow cytometry showed that PTX-PEG-PLGAnp was superior better than PTX in inducing apoptosis in MIAPACA-2 cells. The tpgs emulsification method is simple and environment-friendly. The paclitaxel loaded nanoparticles prepared through the optimization of the formulation have large drug loading capacity and uniform particle size, which can target the pancreatic cancer MIAPACA-2 cells, and do not weaken its ability to inhibit the growth of MIAPACA-2 cells. The nanoparticles also induce apoptosis in cancer MIAPACA-2 cells, and could be used for further clinical treatment of pancreatic cancer.