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.