Efficacy of transferrin-conjugated paclitaxel-loaded nanoparticles in a murine model of prostate cancer

被引:229
作者
Sahoo, SK
Ma, W
Labhasetwar, V [1 ]
机构
[1] Nebraska Med Ctr, Dept Pharmaceut Sci, Omaha, NE 68198 USA
[2] Univ Nebraska, Ctr Med, Dept Biochem & Mol Biol, Omaha, NE 68198 USA
关键词
sustained release; biodegradable polymer; antiproliferative effect; drug delivery; ligand; tumor inhibition;
D O I
10.1002/ijc.20405
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chemotherapy remains the preferred choice of treatment for prostate cancer but modest drug response and significant toxicity by conventional methods of administration limit their efficacy. In our study, we determined the efficacy of paclitaxel (Tx)-loaded biodegradable nanoparticles (NPs) on tumor inhibition. We hypothesized that NPs following conjugation. to transferrin (Tf) ligand (NPs-Tf) would enhance the therapeutic efficacy of the encapsulated drug. The antiproliferative activity of NPs was determined in human prostate cancer cell line (PC3) and their effect on tumor inhibition in a murine model of prostate cancer. NPs (similar to 220 nm in diameter, 5.4% w/w drug loading) under in vitro conditions exhibited sustained release of the encapsulated drug (60% release in 60 days). The IC50 (concentration of drug for 50% inhibition of cell growth) of the drug with Tf-conjugated NPs (Tx-NPs-Tf) was about 5-fold lower than that with unconjugated NPs (Tx-NPs) or drug in solution. Animals that received a single-dose intratumoral injection of Tx-NPs-Tf (Tx dose = 24 mg/kg) demonstrated complete tumor regression and greater survival rate than those that received either Tx-NPs or Tx-Cremophor(R) EL formulation. In conclusion, sustained release NPs demonstrated greater antitumor activity following their conjugation to Tf ligand. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:335 / 340
页数:6
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