Efficacy of transferrin-conjugated paclitaxel-loaded nanoparticles in a murine model of prostate cancer.
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 (approximately 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= 4 mg/kg) demonstrated complete tumor regression and greater survival rate than those that received either Tx-NPs or Tx-Cremophor EL formulation. In conclusion, sustained release NPs demonstrated greater antitumor activity following their conjugation to Tf ligand.
Sahoo
Sanjeeb K
SK
Department of Pharmaceutical Sciences, Nebraska Medical Center, Omaha, NE 68198-6025, USA.
Ma
Wenxue
W
Labhasetwar
Vinod
V
D000818:Animals; D001672:Biocompatible Materials; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D008297:Male; D051379:Mice; D008819:Mice, Nude; D036103:Nanotechnology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology*; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000662:veterinary; D016019:Survival Analysis; D014168:Transferrin / Q000008:administration & dosage / Q000494:pharmacology*
D001672:Biocompatible Materials; D014677:Pharmaceutical Vehicles; D014168:Transferrin; C022131:cremophor; D011092:Polyethylene Glycols; D017239:Paclitaxel