A TPGS-incorporating nanoemulsion of paclitaxel circumvents drug resistance in breast cancer.

Abstract

Paclitaxel resistance is usually developed in clinical chemotherapy, which remains a major obstacle for successful cancer treatment. Herein, we attempted to develop a TPGS incorporating nanoemulsion of paclitaxel (NE-PTX) to circumvent the drug resistance in breast cancer. NE-PTX was prepared by a self-assembly technique and the physicochemical properties were characterized. The efficacy of NE-PTX on overcoming paclitaxel resistance was measured by in vitro and in vivo evaluation. The measured results indicated that NE-PTX was nanometer-sized droplets with the mean diameter of 24.93±3.45 nm. The IC50 value of paclitaxel in resistant MCF-7/ADR cells was greatly reduced from 101.45 μg/mL to 5.39 μg/mL, which indicated that the paclitaxel resistance was effectively reduced by NE-PTX. The reversal of paclitaxel resistance could mainly ascribe to the significant inhibition of P-gp activity and enhancement of anti-cancer activity. Moreover, the tumor volume in resistant tumor xenograft model treated with NE-PTX was only 10.06% of that of paclitaxel solution group, and the tumor inhibitory rate of NE-PTX reached 93.84%, which effectively verified the efficacy of NE-PTX on treating paclitaxel resistance. Thereby, NE-PTX could provide an effective strategy for circumventing paclitaxel resistance in breast cancer.

• Authors: Huihui Bu, Xinyu He, Zhiwen Zhang, Qi Yin, Haijun Yu, Yaping Li
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 471 Issue 1-2 Pg. 206-13 (Aug 25 2014) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 24866272 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents, Phytogenic
• Drug Carriers
• Emulsions
• Vitamin E
• tocophersolan
• Paclitaxel

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (biosynthesis, metabolism)
• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Survival (drug effects)
• Drug Carriers (chemistry)
• Drug Resistance, Neoplasm (drug effects)
• Emulsions
• Humans
• Inhibitory Concentration 50
• MCF-7 Cells
• Mammary Neoplasms, Experimental (drug therapy, metabolism, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Mice, Nude
• Nanostructures (chemistry)
• Paclitaxel (administration & dosage, pharmacology, therapeutic use)
• Vitamin E (chemistry)
• Xenograft Model Antitumor Assays