期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 99, 期 12, 页码 4874-4879出版社
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.22200
关键词
hepatocellular carcinoma; vincristine; verapamil; PLGA nanoparticles; multidrug resistance
资金
- National Natural Science Foundation of China [30901868, 30772668]
- National 863 Project [2007AA021810]
Hpatocellular carcinoma (HCC) is one of the malignant tumors with poor chemosensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR). Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn) were prepared. The entrapment efficiencies of VCR and VRP were 70.92 +/- 3.78% and 85.78 +/- 3.23%, respectively (n = 3). The HCC therapeutic activity of CVn was assessed using MTT assay. In BEL7402 and BEL7402/5-FU human hepatocarcinoma cell lines, CVn had the same antitumor effect as one free drug/another agent-loaded PLGANPs (C+Vn or Cn+V) combination and coadministration of two single-agent- loaded PLGANPs (Cn+Vn), which was slightly higher than that of the free VCR/VRP combination (C-V). CVn might cause lower normal tissue drug toxicity by the enhanced permeation and retention effect in vivo. Additionally, CVn might cause fewer drug-drug interaction and be the most potential formulation to simultaneously deliver VCR and VRP to the target cell in vivo than the other three nanoparticle formulations (C+Vn, Cn+V, and Cn+Vn). Therefore, we speculate that CVn might be the most effective preparation in the treatment of drug-resistant human HCC in vivo. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4874-4879, 2010
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