Biodisposition characteristics of N-succinyl-chitosan and glycol-chitosan in normal and tumor-bearing mice.

Abstract

Two water-soluble chitosan derivatives, N-succinyl-chitosan (Suc-chi; average MW 3x10(5)) and glycol-chitosan (Gly-chi; average MW 1.5x10(5)), were examined concerning their biodisposition characteristics in order to evaluate their possible use as water-soluble drug carriers. Their body distribution and urinary excretion were investigated by i.v. administration of FITC-labeled Suc-chi (FTC-Suc-chi) and FITC-labeled Gly-chi (FTC-Gly-chi) to normal and Sarcoma 180 solid tumor-bearing mice. In normal mice, both polymers showed good retention in blood circulation; especially, FTC-Suc-chi exhibited a long half-life of 51 h, and its distribution to other tissues was very small. FTC-Gly-chi was distributed into the kidney to a relatively high extent. In tumor-bearing mice, FTC-Suc-chi and FTC-Gly-chi were eliminated faster from the blood circulation than in normal mice, that is, with half-lives of 11 and 7 h, respectively. FTC-Suc-chi was less partitioned to the tumor tissue but accumulated more easily into it compared with FTC-Gly-chi. This suggested the enhanced permeability and retention (EPR) effect of Suc-chi and explained the previous result that a water-soluble Suc-chi-mitomycin C conjugate injected intravenously exhibited a good effect against Sarcoma 180 solid tumor. FTC-Gly-chi showed greater distribution to the kidney than in normal mice. Urinary excretion studies indicated the faster excretion of both polymers in tumor-bearing mice. The molecular weight of the products excreted into urine indicated that both polymers should be pretty resistant to the hydrolytic enzyme, lysozyme. Taking toxicities into account, Suc-chi is considered to be available as a drug carrier showing long systemic retention and tumor accumulation.

• Authors: K Kamiyama, H Onishi, Y Machida
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 22 Issue 2 Pg. 179-86 (Feb 1999) ISSN: 0918-6158 [Print] Japan
• PMID: 10077438 (Publication Type: Journal Article)

Chemical References

• N-succinyl-chitosan
• glycol-chitosan
• Chitin
• Chitosan
• Fluorescein

Topics

• Animals
• Chitin (analogs & derivatives, pharmacokinetics, urine)
• Chitosan
• Fluorescein (chemistry)
• Male
• Mice
• Sarcoma, Experimental (metabolism)
• Tissue Distribution