Improved anti-tumor efficiency against prostate cancer by docetaxel-loaded PEG-PCL micelles

J Huazhong Univ Sci Technolog Med Sci. 2014 Feb;34(1):66-75. doi: 10.1007/s11596-014-1233-0. Epub 2014 Feb 6.

Abstract

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Area Under Curve
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Hemolysis / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Micelles*
  • Particle Size
  • Polyesters / chemistry
  • Polyethylene Glycols / chemistry
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Taxoids / chemistry
  • Taxoids / pharmacokinetics
  • Taxoids / pharmacology*
  • Treatment Outcome
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Micelles
  • Polyesters
  • Taxoids
  • Docetaxel
  • polycaprolactone
  • Polyethylene Glycols