具有高效可控传质特性的海藻酸钙凝胶微球的制备研究

Owing to the biocompatibility of calcium alginate hydrogel microparticles，they are widely used as carriers for encapsulation in biomedical area. Efficient and controllable mass transfer characteristics are critical to calcium hydrogel microparticles. The sizes of alginate hydrogel particles prepared by traditional extrusion dripping method are more than one millimeter，which limits the mass transfer efficiency. Recently years, microfluidic method is introduced to prepare calcium alginate hydrogel microparticles about one hundred micrometer with improved the mass transfer efficiency. However, limited by the high viscosity of alginate solution and the size of microchannel, the mass transfer efficiency of calcium alginate hydrogel microparticles are hard to further enhance by decreasing the size. Moreover, the sol-gel progress in preparing calcium alginate hydrogel microparticles is very fast, there is no efficient method reported to control the cross-linking progress at present. This topic proposes an novel approach to prepare calcium alginate hydrogel microparticles with efficient mass transfer characteristics of several microns, and the mass transfer characteristics can be further adjusted by regulated cross-linking react progress. The results will present a novel type of calcium alginate hydrogel carrier with efficient and controllable mass transfer characteristics for microencapsulation. At the same time, the results will provide a new idea for preparing microparticles of several micrometers.

海藻酸钙凝胶微球由于其良好的生物相容性特点而被广泛地用作生物医药领域的微囊化载体。高效可控的传质特性对海藻酸钙凝胶的微囊化功能具有重要的意义。传统液滴挤出法制备的海藻酸钙凝胶微球多为毫米级，传质效率较低。为了提高其传质性能，近年来研究者结合微流控技术制备了尺寸为百微米左右的海藻酸钙凝胶微球。然而，局限于微通道的尺寸和海藻酸盐溶液的粘度，微流控技术难以制备尺寸更小、传质效率更高的海藻酸钙凝胶微球；此外，由于海藻酸钙凝胶微球制备过程的交联反应非常迅速，目前还没有能够有效控制其交联过程的方法报道。本课题提出基于乳化液膜反应体系制备海藻酸钙凝胶微球新方法，该方法不仅能实现尺寸为数微米、具有高效传质特性的海藻酸钙凝胶微球制备，还能进一步对其交联过程进行调控而调节其传质性能。研究结果将为微囊化过程提供具有高效可控传质特性的海藻酸钙凝胶微球载体，同时为制备尺寸为数微米功能微球提供一种新的思路。

海藻酸钙微球微囊由于其良好的生物相容性特点而被广泛地用作生物医药领域的载体。通常采用二价的钙离子作为交联剂与海藻酸钠进行交联制备海藻酸钙微球微囊载体。海藻酸钙微球微囊载体的传质特性受到其尺寸、结构、凝胶网络和形貌等的直接影响，同时包载物活性也受到载体制备工艺的直接影响。研究者提出了多种制备海藻酸钙微球微囊载体的方法，然而由于钙离子与海藻酸钠发生交联反应的过程非常迅速，导致这些方法最终制备得到海藻酸钙微球微囊载体的尺寸和形貌等难以精确的控制，进而使海藻酸钙微囊微球在作为生物医药领域内载体时功能受到极大的限制。为了解决海藻酸钙微球微囊载体在制备过程中尺寸和形貌控制等方面存在的问题，本研究提出了全新的可控制备海藻酸钙微球微囊的方法。（1）基于乳化液膜传质反应制备尺寸为数微米的海藻酸钙微球。该制备海藻酸钙微球载体的方法解决了海藻酸钠溶液粘度大，难以分散成尺寸为数微米级的乳液模板的问题。（2）使用可pH触发释放钙离子水溶性乙二胺四乙酸钙作为的钙源，实现了在温和条件下制备形貌可控的海藻酸钙微囊。使用乙二胺四乙酸钙作为钙源，通过调控溶液的pH值触发乙二胺四乙酸钙释放钙离子交联海藻酸钠，制备的海藻酸钙微囊微球尺寸均一，球形度好且凝胶网络结构均一。该方法解决了海藻酸钙微囊在制备过程中使用紫外光触发可能导致包载物失活，或者是使用纳米碳酸钙作为钙源，微囊的凝胶网络结构不均一，球形度差等问题。这两种全新的海藻酸钙微球微囊的方法为基于海藻酸钙微球微囊的载体的应用提供了重要的技术基础。