Synthesis of Nanoparticles of Star-shaped Mannitol-core PLA-TPGS Copolymer for Delivery of Paclitaxel and Activity of Anti-prostate Cancer†

doi:10.7503/cjcu20140504

Abstract

Abstract:

The objective of this research is to fabricate novel nanoparticles(NPs) of star-shaped mannitol-functionalized polylactic acid-D-α-tocopheryl polyethylene glycol 1000 suclinat(PLA-TPGS) copolymer for paclitaxel delivery for prostate cancer treatment, and evaluate their therapeutic effects in prostate cancer cell line in comparison with the linear PLGA NPs and PLA-TPGS NPs. The paclitaxel-loaded M-PLA-TPGS NPs, prepared by a modified nano-precipitation method, were observed by field emission scanning electron microscopy(FESEM) to be near-spherical shape with narrow size distribution. The drug-loaded NPs were further characterized in terms of size, surface charge, drug content, encapsulation efficiency and in vitro drug release. In vitro drug release exhibited biphasic pattern with initial burst release followed by slow and continuous release. The cellular uptake level of M-PLA-TPGS NPs was demonstrated higher than linear PLGA NPs and PLA-TPGS NPs in PC-3 cells. The data also showed that the paclitaxel-loaded M-PLA-TPGS nanoparticles have higher antitumor efficacy than that of linear PLA-TPGS nanoparticles and commercial Taxol in vitro. The star-shaped copolymer M-PLA-TPGS could be used as a potential and promising molecular biomaterial applied in developing novel nanoformulation for prostate cancer treatment.

Key words: Star-shaped copolymer, Paclitaxel, Polylactic acid, Poly(lactic-co-glycolic acid), Nano-particles, Drug delivery, Cancer nanotechnology, Prostate cancer, Cytotoxicity

CLC Number:

O633.1

TrendMD:

WANG Hai, ZHANG Chao, ZHANG Linhua, LIU Lanxia, ZHENG Yi, ZHU Dunwan. Synthesis of Nanoparticles of Star-shaped Mannitol-core PLA-TPGS Copolymer for Delivery of Paclitaxel and Activity of Anti-prostate Cancer^†[J]. Chem. J. Chinese Universities, 2014, 35(10): 2239.

Figures/Tables 10

Fig.1 Chemical structure of M-PLA-TPGS

Fig.2 1H NMR spectrum of M-PLA-TPGS

Fig.3 Gel permeation chromatogram(GPC) of M-PLA-TPGS copolymer

Fig.4 Thermogravimetric analysis(TGA) curves of M-PLA-TPGS(a) and TPGS(b)

Table 1 Characterization of paclitaxel-loaded nanoparticles*

Sample	Size/nm	PDI	Zeta potential/mV	Loading capacity(%)	EE(%)
PLGA	146.4±4.9	0.211	-24.3±0.1	8.58	84.39
PLA-TPGS	136.9±3.2	0.187	-18.9±0.3	9.13	91.23
M-PLA-TPGS	123.2±2.9	0.159	-13.6±0.8	10.02	98.98

Fig.5 FESEM image of paclitaxel-loaded M-PLA-TPGS NPs

Fig.6 In vitro release profiles of paclitaxel-loaded nanoparticles

Fig.7 CLSM images of PC-3 cells after 4 h incubation with coumarin6-loaded PLA-TPGS(A1—A3) and M-PLA-TPGS NPs(B1—B3) at 37 ℃ (A1, B1) EGFP; (A2, B2) DAPI; (A3, B3) DAPI+EGFP.

Fig.8 Cellular uptake efficiency of coumarin6-loaded NPs in PC-3 cells

Fig.9 Viability of PC-3 cells cultured with paclitaxel-loaded M-PLA-TPGS NPs in comparison with that of Taxol at the same paclitaxel dose and that of PLA-TPGS NPs(n=5) for 24 h(A), 48 h(B) and 72 h(C)

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