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Vitamin E D-alpha-tocopheryl Polyethylene Glycol 1000 Succinate-Conjugated Liposomal Docetaxel Reverses Multidrug Resistance in Breast Cancer Cells

Vitamin E D-alpha-tocopheryl Polyethylene Glycol 1000 Succinate-Conjugated Liposomal Docetaxel Reverses Multidrug Resistance in Breast Cancer Cells

Na Li, Tingting Fu, Wenling Fei, Tianyan Han, Xiangshuai Gu, Yanhui Hou, Yanhua Liu, Jianhong Yang

J Pharm Pharmacol. 2019 Aug;71(8):1243-1254.

PMID: 31215039

Abstract:

Objectives:
Multidrug resistance (MDR) remains a primary challenge in breast cancer treatment. In the present study, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS)-coated docetaxel-loaded liposomes were developed as a novel drug delivery system to reverse MDR and enhance breast cancer therapy compared with the traditional liposomes, DSPE-mPEG-coated liposomes (stealth liposomes) and commercial Taxotere® .
Key findings:
Liposomes were prepared by thin - film dispersion method. Evaluations were performed using human breast cancer MCF-7 and resistant MCF-7/ADR cells. The reversal multidrug-resistant effect was assessed by P-gp inhibition assay, cytotoxicity, cellular uptake and apoptosis assay.
Results:
The TPGS-chol-liposomes were of an appropriate particle size (140.0 ± 6.0 nm), zeta potential (-0.196 ± 0.08 mv), high encapsulation efficiency (99.0 ± 0.9) and favourable in vitro sustained release. The TPGS-coated liposomes significantly improved cytotoxicity and increased the intracellular accumulation of docetaxel in both types of breast cancer cells. The TPGS-coated liposomes were confirmed to induce apoptosis via a synergistic effect between docetaxel and TPGS. It was demonstrated that TPGS enhanced the intracellular accumulation of drug by inhibiting overexpressed P-glycoprotein.
Conclusions:
The TPGS-conjugated liposomes showed significant advantages in vitro compared with the PEG-conjugated liposomes. The TPGS-conjugated liposomes could reverse the MDR and enhance breast cancer therapy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP25322683-A	Polyethylene glycol 1000		25322-68-3	Price

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