Evaluation of antimetastatic activity and systemic toxicity of camptothecin-loaded microspheres in mice injected with B16-F10 melanoma cells

J Pharm Pharm Sci. 2006;9(1):22-31.

Abstract

Purpose: The aim of this work was to evaluate the pulmonary antimetastatic activity and the systemic toxicity of camptothecin-loaded microspheres.

Methods: PCL microspheres containing camptothecin (CPT) were prepared by the emulsion solvent/evaporation method and characterized according to their encapsulation efficiency, particle size, morphology, and drug release. The ability of CPT to inhibit the lung metastasis was verified using an experimental mouse model intravenously injected with metastatic B16- F10 melanoma cells. The microspheres and the free drug were given intraperitoneally at a dose of 7 mg/kg at intervals of three or five days for 24 days. The systemic toxicity of CPT was evaluated by weight measurements, survival and hemograms of the animals.

Results: The encapsulation efficiency was nearly 80%. The drug release was complete after 72 hours, but the burst effect increased from 7% to 35% with the increase in CPT content in the particles. It was observed during the in vivo essays that all groups treated with CPT had a decrease of nearly 70% in the number of lung metastases. However, systemic toxicity was verified in animals that received the free drug.

Conclusion: Camptothecin-loaded microspheres demonstrated similar therapeutic efficacy when compared to those of the free drug, but the toxicity was significantly reduced.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / toxicity
  • Camptothecin / administration & dosage*
  • Camptothecin / toxicity
  • Capsules
  • Delayed-Action Preparations
  • Disease Models, Animal
  • Drug Carriers
  • Drug Delivery Systems*
  • Melanoma / prevention & control*
  • Mice
  • Microspheres
  • Neoplasm Metastasis / prevention & control*
  • Neoplasm Transplantation
  • Particle Size

Substances

  • Antineoplastic Agents, Phytogenic
  • Capsules
  • Delayed-Action Preparations
  • Drug Carriers
  • Camptothecin