Wu Jie, Su Zhi-Guo, Ma Guang-Hui
State Key Lab of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080, China.
Int J Pharm. 2006 Jun 6;315(1-2):1-11. doi: 10.1016/j.ijpharm.2006.01.045. Epub 2006 Apr 17.
The quaternized chitosan was synthesized by the reaction of chitosan and glycidyltrimethylammonium chloride (GTMAC) and named as N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC). A novel hydrogel system composed of HTCC/glycerophosphate (HTCC/GP) with thermo- and pH-sensitivity was synthesized and used as an intelligent drug carrier. The formulation was solution below or at room temperature, which allowed it injectable and to incorporate living cells, proteins, enzymes or other therapeutic drugs easily. Once the surrounding temperature was up to 37 degrees C, the system was transformed to a non-flowing hydrogel, and the formed hydrogel can release the trapped drug as a function of pH values. The swelling behavior of the system and the release profiles of doxorubicin hydrochloride (DX) as a model drug at different pH values were investigated. At acidic condition the hydrogel dissolved and released drug quickly, while it absorbed water and released drug slowly at neutral or basic conditions. Hydrogel composed of chitosan hydrochloride and glycerophosphate (CS/GP) was also prepared to compare with HTCC/GP hydrogel. The HTCC/GP hydrogel in this study was transparent which made it suitable for some specific uses such as ocular drug formulation.
通过壳聚糖与缩水甘油三甲基氯化铵（GTMAC）反应合成了季铵化壳聚糖，并将其命名为N-[(2-羟基-3-三甲基铵)丙基]壳聚糖氯化物（HTCC）。合成了一种由具有温度和pH敏感性的HTCC/甘油磷酸酯（HTCC/GP）组成的新型水凝胶体系，并将其用作智能药物载体。该制剂在低于或等于室温时为溶液，这使其可注射，并易于包载活细胞、蛋白质、酶或其他治疗药物。一旦周围温度升至37℃，该体系转变为不流动的水凝胶，并且形成的水凝胶可根据pH值释放包载的药物。研究了该体系的溶胀行为以及作为模型药物的盐酸多柔比星（DX）在不同pH值下的释放曲线。在酸性条件下，水凝胶溶解并快速释放药物，而在中性或碱性条件下，它吸水并缓慢释放药物。还制备了由壳聚糖盐酸盐和甘油磷酸酯（CS/GP）组成的水凝胶以与HTCC/GP水凝胶进行比较。本研究中的HTCC/GP水凝胶是透明的，这使其适用于一些特定用途，如眼部药物制剂。
