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The antitumor efficacy of functional paclitaxel nanomicelles in treating resistant breast cancers by oral delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
8035 574 2011 18 PDF Available
Title
The antitumor efficacy of functional paclitaxel nanomicelles in treating resistant breast cancers by oral delivery
Abstract

Paclitaxel has shown potent efficacy against a wide spectrum of cancers in clinical treatment. However, chemotherapy with paclitaxel has been limited due to serious allergic reactions in patients caused by cremophor EL, and multidrug resistance in many types of tumors, and the restricted permeability across the intestinal barrier. Functional paclitaxel nanomicelles were developed to overcome these obstacles. Evaluations were performed on the breast cancer MCF-7 and resistant MCF-7/Adr cells, MCF-7 and MCF-7/Adr tumor spheroids, Caco-2 cell manolayers, everted gut sacs and the xenografted resistant MCF-7/Adr cancers in nude mice. The functional paclitaxel nanomicelles were approximately of 15 nm in diameter, significantly increased the intracellular uptake of paclitaxel, and selectively accumulated into mitochondria and endoplasmic reticulum after treatment, showing strong inhibitory effect on MCF-7 and MCF-7/Adr cells. They were able to penetrate deeply into the central region of the MCF-7 and MCF-7/Adr spheroids, resulting in a significant reduction in the size of the spheroids. TEM observations showed that the intact functional paclitaxel nanomicelles were transported across the Caco-2 cell manolayer or the everted gut sac. A significant antitumor efficacy in the xenografted resistant MCF-7/Adr cancers in mice was evidenced by oral administration, which was comparable to intravenous administration. The functional paclitaxel nanomicelles would provide a strategy for oral administration of paclitaxel, increasing solubility of paclitaxel, and overcoming the multidrug resistant cancers.

Keywords
Functional paclitaxel nanomicelles; Oral administration; Transport across the intestinal barrier; Multidrug resistant; Breast cancer
First Page Preview
The antitumor efficacy of functional paclitaxel nanomicelles in treating resistant breast cancers by oral delivery
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 12, April 2011, Pages 3285–3302
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering