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在 NaHCO3 存在下壳聚糖溶液的智能胶凝作用用于可注射药物递送系统。

Smart gelation of chitosan solution in the presence of NaHCO3 for injectable drug delivery system.

机构信息

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China.

出版信息

Int J Pharm. 2011 Jul 29;414(1-2):6-15. doi: 10.1016/j.ijpharm.2011.04.052. Epub 2011 Apr 28.

Abstract

In situ gelling systems are attractive as injectable vehicles for drug delivery. The present work described a novel gelation process of acidic chitosan solution in the presence of sodium bicarbonate (NaHCO(3)). The NaHCO(3) concentration played an important role in this gelling system. When it came within the appropriate range, the chitosan/NaHCO(3) system would stay at sol state in certain condition and showed sol-gel transition from the top to the bottom after heating. The rheological properties of the gelling system, as well as the morphology and erosion behavior of the formed chitosan hydrogels were evaluated as a function of the NaHCO(3) concentration in sols. The hydrogels showed porous morphologies with some diversification depending on the NaHCO(3) concentration, which also affected their erosion behaviors and drug release rates. Moreover, the gelation mechanism of such chitosan/NaHCO(3) system was studied and proposed as the formation of three-dimensional chitosan network with physical junctions thanks to the deprotonation of -NH(3)(+) in chitosan accompanying with the gradual neutralization between HCO(3)(-) and acid. In vivo gelation test was also performed by the dorsal subcutaneous injection of chitosan/NaHCO(3) solution in rat. The formation of in situ gels suggested such system promising applications in injectable drug delivery system.

摘要

原位凝胶系统作为药物传递的可注射载体很有吸引力。本工作描述了一种在碳酸氢钠(NaHCO(3))存在下酸性壳聚糖溶液的新型胶凝过程。NaHCO(3)浓度在该凝胶系统中起着重要作用。当处于适当的范围内时,壳聚糖/NaHCO(3)系统在一定条件下保持溶胶状态,加热后从顶部到底部发生溶胶-凝胶转变。考察了凝胶系统的流变性能以及形成的壳聚糖水凝胶的形态和侵蚀行为与溶胶中 NaHCO(3)浓度的关系。水凝胶具有多孔形态,根据 NaHCO(3)浓度的不同呈现出一定的多样化,这也影响了它们的侵蚀行为和药物释放速率。此外,还研究了这种壳聚糖/NaHCO(3)系统的胶凝机制,并提出了由于壳聚糖中-NH(3)(+)的去质子化以及 HCO(3)(-)和酸之间的逐步中和,形成具有物理交联的三维壳聚糖网络的机制。还通过在大鼠背部皮下注射壳聚糖/NaHCO(3)溶液进行了体内胶凝试验。原位凝胶的形成表明该系统有望在可注射药物传递系统中得到应用。

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