Ta Hang T, Han Han, Larson Ian, Dass Crispin R, Dunstan Dave E
Department of Chemical and Biomolecular Engineering, University of Melbourne, Vic. 3010, Australia.
Int J Pharm. 2009 Apr 17;371(1-2):134-41. doi: 10.1016/j.ijpharm.2009.01.018.
Injectable thermo-activated hydrogels have shown great potential in biomedical applications including use in therapeutic delivery vehicles. In addition to their biocompatibility, the feasibility of these delivery systems is significantly contributed by their ability to gel at physiological conditions and to release entrapped molecules in a sustained manner. In this study, parameters affecting the gelling behavior and the release characteristics of a neutral hydrogel system based on chitosan and an inorganic orthophosphate salt have been investigated. Monobasic and tribasic phosphate salts were not effective in inducing gelation of chitosan solution. However, in the presence of dibasic phosphate salt such as dipotassium hydrogen orthophosphate (DHO), the acidic chitosan solution was neutralized and gelling at temperature and time regulated by varying chitosan and salt concentrations in the formulation. The release rate of the entrapped macromolecules depended on chitosan concentration, DHO concentration, structural conformation and molecular weight of entrapped agents. The relationship between the morphology of the hydrogel and the release profiles are discussed. Chitosan/DHO (Chi/DHO) hydrogels were found to be cytocompatible as evaluated in an in vitro study using a human cell line. These results indicate the potential of Chi/DHO hydrogels as delivery systems for different therapeutic agents with controlled release kinetics.
可注射热活化水凝胶在生物医学应用中展现出了巨大潜力，包括用于治疗性递送载体。除了具有生物相容性外，这些递送系统的可行性还很大程度上得益于它们在生理条件下凝胶化以及持续释放包封分子的能力。在本研究中，对影响基于壳聚糖和无机正磷酸盐的中性水凝胶系统的凝胶化行为和释放特性的参数进行了研究。一元磷酸盐和三元磷酸盐在诱导壳聚糖溶液凝胶化方面无效。然而，在存在二元磷酸盐如磷酸氢二钾（DHO）的情况下，酸性壳聚糖溶液被中和，并在通过改变配方中壳聚糖和盐的浓度来调节的温度和时间下发生凝胶化。包封的大分子的释放速率取决于壳聚糖浓度、DHO浓度、包封剂的结构构象和分子量。讨论了水凝胶的形态与释放曲线之间的关系。在使用人类细胞系的体外研究中评估发现，壳聚糖/ DHO（Chi/DHO）水凝胶具有细胞相容性。这些结果表明Chi/DHO水凝胶作为具有可控释放动力学的不同治疗剂的递送系统的潜力。
