二肽基pH响应型双组分超分子水凝胶及其载药可控释放研究

The supramolecular hydrogels formed by the self-assembly of low molecular mass hydrogelators (LMHGs) via noncovalent interactions have received intensive research attention. However, most of dipeptide-based LMHGs that have been discussed so far are composed from one component small molecule but recently interest in two component hydrogels has increased. In this study, a series of dipeptide-based compounds have been designed, synthesized and tested for gelation as pH-sensitive two-component hydrogelators. The correlation between molecular microstructure of LMHGs and properties of corresponding hydrogels will be probed systematically to find out a well-defined structure–property relationship for the structural guidelines of rational design of new two-component hydrogelators. At the same time, the model molecules with differrent nature are chosen in order to study the influence of additives on self-assembly of dipeptide -based two-component hydrogelators and properties of hydrogels and to tune and control the formation of anisotropy in situ. Behavior and mechanism of sustained release of drug within two-component hydrogel and the “drug-induced” multi-component hydrogels will be also investigated under variou conditions. Furthemore, the biocompatibility of pHsensitive two-component hydrogels is evalulated to enlarge the application range of hydrogels. These results could be used in many areas, such as artificial tissues, drug release matrices, molecular recognition materials, chemical switch and so on.

低分子水凝胶因子自组装而形成的超分子水凝胶已引起广泛关注。然而，目前大多数超分子水凝胶仍由单组分水凝胶因子形成。本项目设计合成二肽基双组分低分子凝胶剂，通过其自组装形成具有pH响应性超分子水凝聚体系。探讨功能性基团微小结构变化对双组分超分子水凝胶结构和功能的影响，弄清分子结构与分子聚集体高级结构之间的关系和聚集体结构与性能的关系，揭示物质多层次构筑的内在规律。改变和调节药物分子类型和大小,研究外加分子对双组分超分子水凝胶自组装过程和性能的影响，实时现场地调控结构各向异性的形成，赋予聚集体相应的性质和功能；构建“药物驱动”的多组分超分子水凝胶体系；研究双组分超分子水凝胶体系内药物分子的可控释放行为、作用机理和调控机制；同时对双组分超分子水凝胶进行生物相容性评价，拓宽超分子凝胶在生物制药领域的应用。本项目将对人造组织、药物控释、分子识别、化学开关等领域的研究提供重要的理论依据。

低分子水凝胶因子自组装而形成的超分子水凝胶已引起广泛关注。然而，目前大多数超分子水凝胶仍由单组分水凝胶因子形成。本项目设计合成二肽基双组分低分子凝胶剂，通过其自组装形成具有pH响应性超分子水凝聚体系。但是，药物的载入后，水凝胶无法形成。糖尿病创面的治疗是全球性的挑战。理论上，改善血管生成和抗菌性对于促进糖尿病创面的愈合至关重要。遗憾的是，尽管目前开发的水凝胶创面敷料本身具有优异的物理特性（保湿、粘性和自愈合能力等），但对于感染或慢性创面的治疗效果（如抗菌、促愈合等）仍然存在明显的不足。在本工作中，为了治疗感染和糖尿病创面，我们设计了一种基于简单分子协调自组装的多功能平台。首先，通过壳聚糖赋予水凝胶载体一定的抗菌能力；并将两种功能性的无机离子（广谱抗菌的Ag+和促进血管生成的Cu2+）引入到水凝胶载体中。实验结果表明，双无机离子与水凝胶的结合，不仅优化了水凝胶的物理性能能，也解决了无机离子本身释放过快的缺陷，最终得到了一种可注射的、具有适当粘性和自愈合性的且兼具长效抗菌和促愈合特性的水凝胶。相应的细菌、细胞以及两种动物实验证实了这种策略的有效性。此外，我们还开发了一种光热、抗菌水凝胶，用于青光眼术后抗瘢痕化治疗。