Anti-tumour and immuno-modulation effects of triptolide-loaded polymeric micelles

Eur J Pharm Biopharm. 2008 Nov;70(3):741-8. doi: 10.1016/j.ejpb.2008.07.017. Epub 2008 Aug 13.

Abstract

Triptolide (TP) possesses both anti-tumour and immuno-suppressive activities. Its immuno-suppressive activity may be disadvantageous for the therapy of cancers. A novel polymeric micelle system containing TP (TP-PM) was constructed by the solvent evaporation method using methoxypolyethylene glycol-poly(d,l-lactic acid)-block copolymer as the carrier, and was characterised using photon correlation spectroscopy, transmission electron microscopy and high performance liquid chromatography. The anti-tumour and immuno-modulation effects of TP-PM were evaluated in sarcoma 180-bearing mice and A2780 cells. Results demonstrated that TP-PM had an average diameter of 78.9 nm, encapsulation efficiency of 66.7%, core-shell morphology and a long-term stability. TP-PM could significantly inhibit tumour growth via intravenous injections at the dose levels of 0.0375, 0.075 and 0.15 mg/kg, and their inhibition rates were 42.5%, 46.0% and 49.9%, respectively; they showed similar cytotoxicity against A2780 cells compared to that of TP. Simultaneously, TP-PM had no effect on the thymus index, spleen index, spleen lymphocyte proliferation and the TNF-alpha and IL-2 levels in serum as compared with TP. Therefore, TP encapsulated in polymeric micelles does not demonstrate immuno-suppressive activity but does not lose its anti-tumour effect. These results show that polymeric micelles are a promising carrier for cancer therapy using TP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / chemistry
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Diterpenes / administration & dosage
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Carriers*
  • Drug Compounding
  • Drug Stability
  • Epoxy Compounds / administration & dosage
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / pharmacology
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / pharmacology*
  • Injections, Intravenous
  • Male
  • Mice
  • Micelles*
  • Particle Size
  • Phenanthrenes / administration & dosage
  • Phenanthrenes / chemistry
  • Phenanthrenes / pharmacology*
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*
  • Sarcoma 180 / drug therapy*
  • Sarcoma 180 / immunology
  • Sarcoma 180 / pathology
  • Solubility
  • Technology, Pharmaceutical / methods
  • Time Factors

Substances

  • Antineoplastic Agents, Alkylating
  • Diterpenes
  • Drug Carriers
  • Epoxy Compounds
  • Immunosuppressive Agents
  • Micelles
  • Phenanthrenes
  • Polyesters
  • methoxy poly(ethylene glycol)-poly(lactide)
  • triptolide
  • Polyethylene Glycols