Kempe Sabine, Metz Hendrik, Bastrop Martin, Hvilsom Annette, Contri Renata Vidor, Mäder Karsten
Martin-Luther-University Halle-Wittenberg, Institute of Pharmaceutics and Biopharmaceutics, Wolfgang-Langenbeck-Strasse 4, Halle/Saale, Germany.
Eur J Pharm Biopharm. 2008 Jan;68(1):26-33. doi: 10.1016/j.ejpb.2007.05.020. Epub 2007 Jul 12.
Chitosan, an amino-polysaccharide, has been proposed as a promising biopolymer for tissue repair and drug delivery. Chitosan solutions containing glycerol-2-phosphate (beta-GP) have been described as injectable in situ gelling thermosensitive formulations, which undergo sol-gel transition at physiological pH and temperatures. This feature makes them suitable for the parenteral administration of drugs, especially for peptides and proteins. The aim of the present study was to get a deeper insight into the macro- and microstructure of chitosan/beta-GP systems. In addition to oscillating rheology, electron paramagnetic resonance (EPR) spectroscopy was applied to examine the microviscosity and pH inside the gels depending on the beta-GP concentration and to follow the loading and release of spin-labelled Insulin. All chitosan/beta-GP solutions showed a physiological pH ranging from 6.6 to 6.8 that did not change during gelation, irrespective of the proportion of beta-GP. The dynamics of the spin-labelled Insulin and its microviscosity inside the gels and during release were monitored by EPR spectroscopy. The results indicate that the Insulin was incorporated into the aqueous environment of the gel and was released in its native form. The in vitro drug release from the gels was governed by diffusion of drug from the gel matrix. A sustained release of Insulin was observed over a period of 2 weeks. Increasing the proportion of beta-GP increased the amount of released Insulin and the velocity thereof.
壳聚糖是一种氨基多糖，已被认为是一种有前景的用于组织修复和药物递送的生物聚合物。含甘油-2-磷酸（β-GP）的壳聚糖溶液已被描述为可注射的原位凝胶化热敏制剂，其在生理pH值和温度下会发生溶胶-凝胶转变。这一特性使其适用于药物的肠胃外给药，尤其是肽和蛋白质类药物。本研究的目的是更深入地了解壳聚糖/β-GP系统的宏观和微观结构。除了振荡流变学外，还应用电子顺磁共振（EPR）光谱来检测凝胶内部的微粘度和pH值（取决于β-GP浓度），并追踪自旋标记胰岛素的负载和释放情况。所有壳聚糖/β-GP溶液的生理pH值范围为6.6至6.8，在凝胶化过程中不会改变，与β-GP的比例无关。通过EPR光谱监测凝胶内部及其释放过程中自旋标记胰岛素的动力学及其微粘度。结果表明，胰岛素被纳入凝胶的水环境中并以其天然形式释放。凝胶的体外药物释放受药物从凝胶基质中的扩散控制。观察到胰岛素在2周内持续释放。增加β-GP的比例会增加胰岛素的释放量及其释放速度。
