Development of novel chitosan derivatives as micellar carriers of taxol

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 grou ps to provide the hydrophilic moieties (N-lauryl-carboxymethyl-chitosan = L CC), was newly synthesized. The solubility of taxol in LCC micelles in aque ous solution was examined. The hemolysis test of LCC and the growth inhibit ion 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 p article sizes less than 100 nm. This particle size was considered effective for passive targeting for tumors. The concentration of taxol in the micell ar solution was very high, with a maximum of 2.37 mg/mL. This maximum was 1 000 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 dam age. As judged by cytostatic activity against KB cells, taxol retained acti vity even when included in LCC micelles. LCC-entrapped taxol was more effec tive 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 carrie r of taxol.