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

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.
AuthorsMing-Ji Jin, Sheng-Jun Piao, Tie-Xiong Jin, Zhe-Hu Jin, Xue-Zhe Yin, Zhong-Gao Gao
JournalJournal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban (J Huazhong Univ Sci Technolog Med Sci) Vol. 34 Issue 1 Pg. 66-75 (Feb 2014) ISSN: 1672-0733 [Print] China
PMID24496681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Micelles
  • Polyesters
  • Taxoids
  • Docetaxel
  • polycaprolactone
  • Polyethylene Glycols
Topics
  • Animals
  • Antineoplastic Agents (pharmacokinetics, 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, pathology)
  • Rats
  • Rats, Sprague-Dawley
  • Taxoids (chemistry, pharmacokinetics, pharmacology)
  • Treatment Outcome
  • Tumor Burden (drug effects)
  • Xenograft Model Antitumor Assays

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