Biomedical subjects

Yoshiharu Machida

Publications and source records attributed to Yoshiharu Machida.

39 records · Page 3Linked to original sources

PubMed2002

Prolonged intestinal absorption of cephradine with chitosan-coated ethylcellulose microparticles in rats.

Cephradine-containing ethylcellulose microparticles (MPC) were prepared by the solvent evaporation method. Chitosan-coated MPC (Chi-MPC) were prepared by doping MPC with viscous chitosan solution and subsequently drying. When fluorescein isothiocyanate (FITC)-labeled chitosan-coated ethylcellulose microparticles without drug were administered intraduodenally, they moved slowly in the intestine, that is, most of them were retained at the upper and middle parts of the small intestine for more than 8 h, which is considered due to mucoadhesive properties of coated chitosan. When MPC and Chi-MPC was incubated at 37 degrees C in the JP 14 second fluid, pH 6.8, both released the drug slowly with similar release rates. Cephradine solution and suspension, MPC and Chi-MPC were administered intraduodenally to investigate intestinal drug absorption. Only Chi-MPC suppressed the initial plasma level and maintained the plasma concentration for a long time up to 24 h, suggesting Chi-MPC would be useful for prolonged intestinal absorption of cephradine.

Animals↗

PubMedDate not supplied

Tumour cell uptake of lactosaminated and intact N-succinyl-chitosans and antitumour effects of conjugates with mitomycin C.

BACKGROUND: The relationship between the uptake of lactosaminated and intact N-succinyl-chitosans into hepatoma cells (MH134 and AH130) and liver metastatic tumour model cells (M5076) and the antitumour effects of their conjugates with mitomycin C (MMC) were investigated. MATERIALS AND METHODS: Fluorescently-labelled carriers were administered to tumour-bearing mice. The fluorescence intensity and microscopic examinations were performed at 1 hour post-injection. The antitumour effects were examined according to several schedules: one of them was the administration of each conjugate at a dose of 4 mg eq. MMC/kg x 4 days at 3 days post-inoculation. RESULTS: A difference in uptake was found by measurement of fluorescence intensity between both carriers only in MH134 cells, but was not recognized by fluorescence microscopy. Among these cell lines, the uptake of carriers into M5076 cells tended to be the most extensive. The difference in antitumour effects of the conjugates against MH134 and M5076 was reflected by the biodistribution study. CONCLUSION: The pattern of antitumour effects was markedly different among cell lines of different origins.

Animals↗

PubMedDate not supplied

Contribution of chitosan and its derivatives to cancer chemotherapy.

The conjugates of some kinds of anticancer agents with chitin and chitosan derivatives display good anticancer effects with a decrease in the adverse effects of the original drug due to a predominant distribution into the cancer and a gradual release of free drug from the conjugates. For instance, doxifluridine and 1-beta-D-arabinofuranosylcytosine (Ara-C) were conjugated with chitosan via glutaric spacer, and the conjugates of Ara-C with chitosan, in particular, showed a good antitumour effect against P388-bearing leukemia model mice. Glycol-chitosan (G-Chi) was distributed mainly in the systemic circulation and the kidney after i.v. administration into normal mice, and retained long in the kidney. The therapeutic effect of the conjugates of mitomycin C (MMC) with G-Chi was not necessarily improved in comparison with that of the free drug, but toxic side-effects appeared to decrease with the conjugates. The conjugates of MMC with 6-O-carboxymethyl-chitin showed almost complete suppression of tumour growth at 10 mg eq. MMC/kg, though a lethal adverse effect was also observed. The conjugates of MMC with N-succinyl-chitosan showed good antitumour activities against various tumour models due to their predominant distribution into the tumour tissue and sustained-release characteristics, irrespective of water-insoluble and -soluble formulations. It is believed that the chitin and chitosan derivatives discussed in this review are good candidates for a polymeric drug carrier in cancer chemotherapy.

Animals↗