Nanoparticles of Poly(Lactide-Co-Glycolide)-d-a-Tocopheryl Polyethylene Glycol 1000 Succinate Random Copolymer for Cancer Treatment

Abstract

Cancer is the leading cause of death worldwide. Nanomaterials and nanotechnologies could provide potential solutions. In this research, a novel biodegradable poly(lactide-co-glycolide)-d-a-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) random copolymer was synthesized from lactide, glycolide and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) by ring-opening polymerization using stannous octoate as catalyst. The obtained random copolymers were characterized by 1H NMR, FTIR, GPC and TGA. The docetaxel-loaded nanoparticles made of PLGA-TPGS copolymer were prepared by a modified solvent extraction/evaporation method. The nanoparticles were then characterized by various state-of-the-art techniques. The results revealed that the size of PLGA-TPGS nanoparticles was around 250 nm. The docetaxel-loaded PLGA-TPGS nanoparticles could achieve much faster drug release in comparison with PLGA nanoparticles. In vitro cellular uptakes of such nanoparticles were investigated by CLSM, demonstrating the fluorescence PLGA-TPGS nanoparticles could be internalized by human cervix carcinoma cells (HeLa). The results also indicated that PLGA-TPGS-based nanoparticles were biocompatible, and the docetaxel-loaded PLGA-TPGS nanoparticles had significant cytotoxicity against Hela cells. The cytotoxicity against HeLa cells for PLGA-TPGS nanoparticles was in time- and concentration-dependent manner. In conclusion, PLGA-TPGS random copolymer could be acted as a novel and promising biocompatible polymeric matrix material applicable to nanoparticle-based drug delivery system for cancer chemotherapy.

Keywords: Cancer chemotherapy; Docetaxel; HeLa; Nanoparticle; PLGA-TPGS; Random copolymer.

Figure 1

Schematic description of the synthesis of PLGA-TPGS random copolymer

Figure 2

FTIR spectra of PLGA-TPGS random copolymer and TPGS

Figure 3

Typical ¹H-NMR spectra of PLGA-TPGS random copolymer and TPGS

Figure 4

Typical GPC chromatograms of PLGA-TPGS random copolymer and TPGS

Figure 5

Thermogravimetric profiles of PLGA-TPGS random copolymer and TPGS

Figure 6

FESEM images of docetaxel-loaded nanoparticles with 0.03% TPGS as emulsifier and 10% drug loading. a, Docetaxel-loaded PLGA nanoparticles; b, docetaxel-loaded PLGA-TPGS nanoparticles

Figure 7

DSC thermograms of pure docetaxel, docetaxel-loaded PLGA-TPGS nanoparticles and docetaxel-loaded PLGA nanoparticles

Figure 8

In vitro drug release profiles of docetaxel-loaded PLGA and PLGA-TPGS nanoparticles

Figure 9

Confocal laser scanning microscopy (CLSM) images of HeLa cells after 4-h incubation with coumarin-6–loaded PLGA-TPGS nanoparticles at 37.0°C. The cells were stained by DAPI (blue) and the coumarin-6–loaded nanoparticles are green. The cellular uptake was visualized by overlaying images obtained by EGFP filter and DAPI filter: left image from EGFP channel (a); center image from DAPI channel (b); right image from combined EGFP channel and DAPI channel (c)

Figure 10

Cytotoxicity of Hela cells cultured with drug-free nanoparticles and docetaxel-loaded PLGA-TPGS nanoparticles containing 0.25, 2.5, 12.5 or 25 μg/ml docetaxel concentrations after 24-, 48- and 72-h cell culture. (n = 3)