College of Marine Life Sciences, Ocean University of China, Qingdao 266003, People's Republic of China.
Biomacromolecules. 2010 Jun 14;11(6):1527-33. doi: 10.1021/bm100158p.
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.
羧甲基壳聚糖（CM-壳聚糖）是壳聚糖的一种水溶性衍生物，作为一种新型生物医学材料备受关注。为了其潜在的应用，对该材料的安全性研究是有说服力的。本研究旨在评估 CM-壳聚糖在大鼠体内的组织分布、药代动力学、生物降解机制和排泄情况。大鼠以 50mg/kg 的剂量腹腔注射荧光素异硫氰酸酯（FITC）标记的 CM-壳聚糖后，迅速吸收并分布到不同的器官，包括肝、脾和肾。CM-壳聚糖在肝中的含量最高。肝中 CM-壳聚糖的水平为 1.6±0.6mg/肝，约占注射的 FITC-CM-壳聚糖总量的 10-22%。尿液排泄是 FITC 标记的 CM-壳聚糖的主要排泄途径，11 天内 85%的剂量通过尿液排泄。通过凝胶色谱法分析体内分布的 FITC-CM-壳聚糖和尿液排泄的 FITC-CM-壳聚糖的分子量。结果表明，FITC-CM-壳聚糖在腹水降解。吸收的 CM-壳聚糖形成物具有相对较高的分子量（约 300kDa），而尿液排泄的 FTC-CM-壳聚糖的分子量小于 45kDa。体外研究表明，CM-Chi 在血浆和肝匀浆中也可降解。在 37℃下孵育 24 小时后，分子量约为 800k 的 CM-壳聚糖在肝匀浆中被彻底降解为小分子。结果表明，肝脏在 CM-壳聚糖的生物降解中起着核心作用。CM-壳聚糖具有良好的生物降解性，可能有助于其临床应用。研究结果还为进一步修饰 CM-壳聚糖作为术后和其他生物医学材料提供了重要线索。
