Enhanced tumor targeting and antitumor efficacy via hydroxycamptothecin-encapsulated folate-modified N-succinyl-N'-octyl chitosan micelles

J Pharm Sci. 2013 Apr;102(4):1318-32. doi: 10.1002/jps.23470. Epub 2013 Feb 11.


10-Hydroxycamptothecin (HCPT) is an effective anticancer drug against various types of solid tumors. But the antitumor efficacy of HCPT is far from satisfactory because of its poor physicochemical properties, short circulating half-life, low stability, and nonspecific toxicity to normal tissues. Therefore, a targeted delivery strategy for HCPT to pathological sites is eagerly needed to overcome these limitations. The folate-modified N-succinyl-N'-octyl chitosan (folate-SOC) micelle was chosen in this study and served as the targeted delivery system for HCPT to improve the antitumor efficacy. The water-insoluble anticancer drug HCPT was encapsulated into the folate-SOC micelles by the dialysis method. The near-spherical HCPT-loaded folate-SOC (HCPT/folate-SOC) micelles were formed in aqueous media with diameter of about 100-200 nm. The HCPT/folate-SOC micelles displayed a good stability, reasonable drug-loading content (about 10%), and sustained release behavior for the water-insoluble HCPT. Compared with free HCPT, HCPT/folate-SOC micelles exhibited a significant enhancement of cellular uptake, higher cytotoxicity against folate receptor positive tumor cell (Bel-7402), excellent tumor-targeting capability and substantially better antitumor efficacy on the nude mice bearing Bel-7402 xenografts. These results demonstrate the potential of folate-SOC micelles as long-term stable and effective drug delivery systems in cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacokinetics
  • Camptothecin / therapeutic use
  • Cell Line, Tumor
  • Chitosan / analogs & derivatives*
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Folic Acid / analogs & derivatives*
  • Humans
  • Mice
  • Mice, Nude
  • Micelles*
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Rats


  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Micelles
  • Chitosan
  • Folic Acid
  • 10-hydroxycamptothecin
  • Camptothecin