Antitumoral activity of camptothecin-loaded nanoparticles in 9L rat glioma model

Int J Pharm. 2011 Jan 17;403(1-2):201-6. doi: 10.1016/j.ijpharm.2010.10.015. Epub 2010 Oct 15.


Camptothecin (CPT), a plant alkaloid, is a potent anticancer drug in cell culture studies but it is clinically inactive due to rapid hydrolysis under physiological conditions. The drug exists in two forms depending on the pH value, an active lactone form at pH below 5 and an inactive carboxylate form at basic pH and this is a reversible reaction. In this study, nanoparticulate delivery systems were developed with either amphiphilic cyclodextrins, poly(lactide-co-glycolide) or poly-ɛ-caprolactone in order to maintain the active lactone form and prevent the drug from hydrolysis. All nanoparticles were prepared with nanoprecipitation technique. Mean particle sizes were 130-280nm and surface charges were negative. The encapsulation efficiency was significantly higher for amphiphilic cyclodextrin nanoparticles when compared to polymeric nanoparticles. Nanoparticle formulations based on cyclodextrins showed a controlled release profile extended up to 12 days. 6-O-Capro-β-cyclodextrin (1.44μg/60μL CPT) and concentrated 6-O-Capro-β-cyclodextrin (2.88μg/60μL CPT) nanoparticles significantly modified the growth or lethality of the 9L gliomas, since the median survival time was 26 days for the untreated group and between 27 and 33 days for amphiphilic cyclodextrin nanoparticle groups. These results indicate that, CPT-loaded amphiphilic cyclodextrin nanoparticles may provide a promising carrier system for the effective delivery of CPT in comparison to polymeric analogues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Camptothecin / administration & dosage
  • Camptothecin / therapeutic use*
  • Cell Line, Tumor
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Female
  • Glioma / drug therapy*
  • Lactic Acid / chemistry
  • Nanoparticles / chemistry*
  • Neoplasm Transplantation
  • Particle Size
  • Polyesters / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Inbred F344
  • Surface-Active Agents / chemistry
  • beta-Cyclodextrins / chemistry


  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Polyesters
  • Surface-Active Agents
  • beta-Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • polycaprolactone
  • Polyglycolic Acid
  • Lactic Acid
  • Camptothecin