Department of Pharmaceutics and Biopharmaceutics, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
J Biomed Mater Res A. 2009 Nov;91(2):324-30. doi: 10.1002/jbm.a.32211.
Chitosan is an attractive biopolymer for the preparation of hydrogels. Its unique combination of biocompatibility, biodegradability, bioadhesivity, and tissue-promoting abilities allows pharmaceutical applications. We investigated novel thermosensitive hydrogels based on chitosan homogeneously reacetylated to a deacetylation degree of about 50%, combined with selected polyols or polyoses such as trehalose, a nontoxic polysaccharide. The latter, a gel-inducing and lyoprotective agent enabled the formulation to be lyophilized and rehydrated without affecting the thermosensitive behavior. This made possible long-term storage and promoted its use in a clinical setup. The thermally induced sol-gel transition allowed injectability and in situ setting. Rheological characterization revealed that storage moduli could be increased by one decade by increasing the chitosan concentration from 1.4 to 2.2% (w/w). Evaluation in vivo provided evidence of in situ implant formation in subcutaneous tissue of Sprague-Dawley rats and permanence for up to 3 months. Histopathological analysis demonstrated a mild, chronic, inflammatory reaction that disappeared with the complete absorption of the gel implant over a few months period. Such in situ forming hydrogels could be advantageous for specific applications in drug delivery and tissue engineering.
壳聚糖是一种有吸引力的生物聚合物，可用于制备水凝胶。其独特的生物相容性、可生物降解性、生物粘附性和组织促进能力使其在药物应用中具有优势。我们研究了基于壳聚糖的新型温敏水凝胶，壳聚糖均匀再乙酰化至脱乙酰度约为 50%，与选定的多元醇或多糖（如海藻糖）结合，海藻糖是一种无毒多糖，具有凝胶诱导和冷冻保护作用，使制剂可以进行冷冻干燥和再水合，而不会影响温敏行为。这使得长期储存成为可能，并促进了其在临床环境中的应用。热诱导的溶胶-凝胶转变允许可注射和原位设置。流变特性表明，通过将壳聚糖浓度从 1.4%（w/w）增加到 2.2%（w/w），可以将储能模量提高一个数量级。体内评估提供了证据表明，在 Sprague-Dawley 大鼠的皮下组织中可以原位形成植入物，并持续长达 3 个月。组织病理学分析表明，存在轻度、慢性炎症反应，随着凝胶植入物在几个月内完全吸收，该反应会消失。这种原位形成的水凝胶可能在药物输送和组织工程的特定应用中具有优势。
