Preparation and Antitumor Effect of N-Trimethylchitosan/Fucoidan Ion-Complex Submicron Particles

Kazuya      Hayashi; Masanaho      Sasatsu; Yoshiharu      Machida; Hiraku      Onishi

doi:10.2174/157341311796196862

Abstract

The aim of this study was to develop a delivery system to enable the promotion of the antitumor potential of fucoidan (FUC). FUC/N-trimethylchitosan (TMC) ion-complex submicron particles (FUC/TMC-SMP) were produced by ionic complexation, and their particle characteristics were investigated. Antitumor effect was examined in vivo using sarcoma 180-bearing mice by oral administration, and body weight loss was checked as an index of toxic side effects. FUC/TMC-SMP could be obtained by the complexation of negatively charged fucoidan with positively charged N-trimethylchitosan under aqueous conditions. The mean particle size was 325 nm and mean FUC content was 47 % (w/w). Oral administration was conducted using two treatment schedules, that is, pre- and post-tumor inoculation. As to pre-treatment, oral administration was performed from 13 days before inoculation to 1 day before inoculation every other day. For post-treatment, preparation samples were administered orally from 1 day after inoculation to 13 days after inoculation every other day. FUC/TMC-SMP were more effective than FUC solution and suppressed tumor growth significantly in both treatment schedules. FUC/TMC-SMP are suggested to be a useful oral delivery system enhancing the antitumor potential of FUC.

Keywords: Ion-complex submicron particles, fucoidan, N-trimethylchitosan, antitumor effect, oral administration, treatment schedule, Submicron particles, Ionic complexation, Particle characteristics, Pre-treatment, Post-treatment, Sarcoma 180, Toxic side effect