Pharmaceutical Research

, Volume 15, Issue 12, pp 1844–1850

Development of Novel Chitosan Derivatives as Micellar Carriers of Taxol

Authors

  • Akio Miwa
    • Pharmaceutics Laboratory, Pharmaceutical Research LaboratoriesTaisho Pharmaceutical Co., LTD
  • Atsuo Ishibe
    • Pharmaceutics Laboratory, Pharmaceutical Research LaboratoriesTaisho Pharmaceutical Co., LTD
  • Mari Nakano
    • Pharmaceutics Laboratory, Pharmaceutical Research LaboratoriesTaisho Pharmaceutical Co., LTD
  • Tomohiro Yamahira
    • Pharmaceutics Laboratory, Pharmaceutical Research LaboratoriesTaisho Pharmaceutical Co., LTD
  • Shigeru Itai
    • Pharmaceutics Laboratory, Pharmaceutical Research LaboratoriesTaisho Pharmaceutical Co., LTD
  • Shuji Jinno
    • Central Research LaboratoryNippon Suisan Kaisha, LTD
  • Hiroyuki Kawahara
    • Central Research LaboratoryNippon Suisan Kaisha, LTD
Article

DOI: 10.1023/A:1011901921995

Cite this article as:
Miwa, A., Ishibe, A., Nakano, M. et al. Pharm Res (1998) 15: 1844. doi:10.1023/A:1011901921995

Abstract

Purpose. To develop an intravenous injectable carrier composed of chitosan derivatives for taxol.

Methods. A chitosan with lauryl groups attached to amino groups to provide the hydrophobic moieties and, carboxymethyl groups attached to hydroxy groups to provide the hydrophilic moieties (N-lauryl-carboxymethyl-chitosan = LCC), was newly synthesized. The solubility of taxol in LCC micelles in aqueous solution was examined. The hemolysis test of LCC and the growth inhibition experiment of taxol-loading micelle using KB cells were also performed as in vitro assay.

Results. It was found that LCC solubilized taxol by forming micelles with particle sizes less than l00nm. This particle size was considered effective for passive targeting for tumors. The concentration of taxol in the micellar solution was very high, with a maximum of 2.37mg/ mL. This maximum was 1000 times above that in a saturated solution of taxol at pH 7.4. Hemolysis testing as an in vitro assay indicated that LCC was safer than Polysorbate 80 (TO-10M) as intravenous surfactant in terms of induction of membrane damage. As judged by cytostatic activity against KB cells, taxol retained activity even when included in LCC micelles. LCC-entrapped taxol was more effective in cytostatic activity than free taxol in low concentrations.

Conclusions. The results of solubilization capacity examination, hemolysis testing, and cytostatic activity suggest that LCC may be useful as a carrier of taxol.

taxolN-lauryl-carboxymethyl-chitosan(LCC)chitosanpolymer micellesolubilitynanoparticlehemolysisantitumor activity

Copyright information

© Plenum Publishing Corporation 1998