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Chitosan-g-TPGS nanoparticles for anticancer drug delivery and overcoming multidrug resistance.

Abstract：

:To overcome the P-glycoprotein (P-gp)-induced multidrug resistance (MDR) of cancer cells, a novel copolymer, chitosan-graft-D-α-tocopheryl polyethylene glycol 1000 (TPGS) (CT) was synthesized for doxorubicin (DOX) delivery by the P-gp inhibiting virtue of TPGS. DOX-loaded CT nanoparticles (NPs) were fabricated by a modified solvent extraction/evaporation method combined with ionic cross-linking to form a uniform particle size of 140-180 nm with ∼40% DOX loading efficiency. These drug-loaded CT NPs demonstrated a pH-responsive release behavior, and DOX was released more quickly under low pH values. Significant cell cytotoxicity was observed on the human hepatocarcinoma cells (HepG2 and BEL-7402) and human breast adenocarcinoma cells (MCF-7). The cell cytotoxicity and apoptosis of drug-resistant cells (MCF-7/DOX and BEL-7402/5-Fu), was greatly enhanced as compared to Adriamycin. The IC50 value showed that DOX-loaded CT NPs could be 1.5-199-fold more effective than Adriamycin. This can be attributed to the P-gp blocking and down-regulation of ATP levels by the CT NPs. The potential of these NPs to act as an oral delivery system was also investigated. Both the pharmacokinetic properties and in vivo antitumor activity of DOX-loaded CT NPs were improved compared with Adriamycin.

journal_name

Mol Pharm

journal_title

Molecular pharmaceutics

authors

Guo Y,Chu M,Tan S,Zhao S,Liu H,Otieno BO,Yang X,Xu C,Zhang Z

doi

10.1021/mp400514t

subject

Has Abstract

pub_date

2014-01-06 00:00:00

pages

59-70

issue

1

eissn

1543-8384

issn

1543-8392

journal_volume

11

pub_type

杂志文章

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