PUBLICATION

Improving the anti-ovarian cancer activity of docetaxel with biodegradable self-assembly micelles through various evaluations

Authors
Gao, X., Wang, S., Wang, B., Deng, S., Liu, X., Zhang, X., Luo, L., Fan, R., Xiang, M., You, C., Wei, Y., Qian, Z., Guo, G.
ID
ZDB-PUB-170214-193
Date
2015
Source
Biomaterials   53: 646-58 (Journal)
Registered Authors
Keywords
Cell apoptosis, Cell growth, Docetaxel, MPEG-PCL, Ovarian cancer, Self-assembly
MeSH Terms
  • Animals
  • Antineoplastic Agents/administration & dosage
  • Antineoplastic Agents/pharmacokinetics
  • Antineoplastic Agents/therapeutic use*
  • Apoptosis
  • Cell Division
  • Cell Line, Tumor
  • Computer Simulation
  • Drug Carriers
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Micelles*
  • Ovarian Neoplasms/drug therapy*
  • Ovarian Neoplasms/pathology
  • Taxoids/administration & dosage
  • Taxoids/pharmacokinetics
  • Taxoids/therapeutic use*
  • Zebrafish
PubMed
25890760 Full text @ Biomaterials
Abstract
Docetaxel (DOC) produces anti-tumor effects by inducing apoptosis and inhibiting cell growth. However, its clinical application is limited by its hydrophobicity and low biocompatibility. Therefore, improving DOC's water solubility, biocompatibility, and anti-tumor effects are important goals that will improve its clinical utility. In this work, DOC and methoxy poly(ethylene glycol) (MPEG)/polycaprolactone (PCL) (MPEG-PCL) showed good compatibility through computer simulations. We prepared DOC-loaded polymeric micelles (DOC/MPEG-PCL micelles) with drug loading of 6.82% and encapsulation efficiency of 98.36%; these were monodispersed and approximately 30 nm in diameter, and released DOC over an extended period in vitro and in vivo. In addition, DOC/MPEG-PCL micelles inhibited cell growth and induced apoptosis more effectively than free DOC in vitro. Furthermore, DOC/MPEG-PCL micelles inhibited ovarian tumor growth more significantly than free DOC. Immunohistochemical analysis indicated that DOC/MPEG-PCL micelles improved DOC's anti-tumor effect by enhancing tumor cell apoptosis and suppressing tumor cell proliferation. Moreover, in bio-imaging analysis, DOC/MPEG-PCL micelles showed a higher concentration and a longer retention time in ovarian tumor tissue than did free DOC, indicating that the DOC/MPEG-PCL micelles delivered more anti-tumor drug to the tumor. Our data suggest that DOC/MPEG-PCL micelles have the potential to be applied clinically in ovarian cancer therapy.
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