Effects of molecular weights on the absorption, distribution and urinary excretion of intraperitoneally administrated carboxymethyl chitosan in rats.

Carboxymethyl chitosan (CM-chitosan) is one of water-soluble derivatives of chitosan. Numerous studies have been focused on its applications as pharmaceutical excipient, bioactive reagent and nontoxic drug carrier. Like other polysaccharides, CM-chitosan is inhomogenous in molecular weight. Originations and preparation procedures considerably influence its molecular weight and molecular weight distributions. Understanding the molecular weight related biological behaviour of this inhomogenous glycopolymer in vivo were crucial for the quality control and clinical applications of chitosan and chitosan based medical devices. In this study, we investigated the effects of molecular weights on the absorption, distribution, degradation and urinary excretion of the fluorescein isothiocyanate-labeled CM-chitosan in rats. The results indicated that molecular weight significantly influenced the uptake of CM-chitosan from the lumen of abdomen and blood vessels to peripheral tissues, the distribution of this chemical and urinary excretion after intraperitoneal administration. These findings provided an important reference for the clinical applications of this versatile derivative of chitosan as postsurgical and other biomedical materials and important clues for the exploitation of CM-chitosan based drug targeting and delivery systems.

Pharmacokinetics and biodegradation mechanisms of a versatile carboxymethyl derivative of chitosan in rats: in vivo and in vitro evaluation.

Carboxymethyl chitosan (CM-chitosan), which is a water-soluble derivative of chitosan, has attracted much attention as a new biomedical material. The safety study of this material was persuasive for its potential application. The present study was conducted to assess the tissue distribution, pharmacokinetics, biodegradation mechanism, and excretion of CM-chitosan in rats. After the rats were intraperitoneally injected at the dose of 50 mg/kg, the fluorescein isothiocyanate (FITC)-labeled CM-chitosan was absorbed rapidly and distributed to different organs, including liver, spleen, and kidney. The highest level of CM-chitosan was found in liver. It was at the level of 1.6 +/- 0.6 mg/liver and made up approximately 10-22% of the total injected FTC-CM-chitosan. Urinary excretion was the predominant way of excretion of FITC-labeled CM-chitosan, and 85% of the dose was excreted in urine over the period of 11 days. The molecular weights of body distributed FTC-CM-chitosan and urinary excreted FTC-CM-chitosan were analyzed by gel chromatography. The results indicated that the FTC-CM-chitosan was degraded in abdominal dropsy. The absorbed CM-chitosan forms were found with a relatively high molecular weight (approximately 300 kDa), whereas the molecular weight of the urinary excreted FTC-CM-chitosan was less than 45 kDa. In vitro research revealed that the CM-Chi was also degradable in plasma and homogenate of liver. The CM-chitosan with a molecular weight of approximately 800k was thoroughly degraded to a small molecule after it was incubated in homogenate of liver at 37 degrees C for 24 h. The results suggested that the liver plays a central role in biodegradation of CM-chitosan. The excellent biodegradability of CM-chitosan could potentially contribute to the clinical applications. The results also provide important clues for further modification of CM-chitosan as the postsurgical and other biomedical materials.