School of Chemical Engineering and Technology, Shanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi'an Jiao Tong University, Xi'an, 710049, P. R. China.
Biomater Sci. 2018 Mar 26;6(4):820-826. doi: 10.1039/c7bm00993c.
Herein, we reveal a double emulsion method combining the sol-gel method to prepare poly(lactic-co-glycolic acid) microspheres with different porous structures for sequential release of two types of biomolecules. By controlling the ripening time of the emulsion, multiple interconnected chambers could be easily chosen to be either embedded in microspheres or opened to the surface. These two types of microspheres exhibited different kinetics for the release of both small molecules and proteins, where the release from microspheres with open pores (5 day over 90%) was much faster than the release from microspheres with embedded pores (25 day over 90%). After loading with interleukin-4 (IL-4) and melatonin, these microspheres were further encapsulated in a sodium alginate hydrogel to form a patch for cutaneous regeneration. The prepared patch was able to recruit alternatively activated (M2) macrophages in the early stage (fast release of IL-4) and promote the growth of blood vessels in the long term (slow release of melatonin), resulting in significantly enhanced cutaneous regeneration. These results also demonstrate the potential of this novel delivery system to deliver multiple therapeutics and achieve synergistic effects.
在此，我们揭示了一种双重乳液方法，结合溶胶-凝胶法来制备具有不同多孔结构的聚（乳酸-共-乙醇酸）微球，用于两种类型生物分子的顺序释放。通过控制乳液的陈化时间，可以轻松选择将多个相互连接的腔室嵌入微球中或打开到表面。这两种类型的微球在小分子和蛋白质的释放动力学上表现出不同的特点，其中具有开放孔的微球（5 天内释放超过 90%）的释放速度明显快于具有嵌入式孔的微球（25 天内释放超过 90%）。在负载白细胞介素 4 (IL-4) 和褪黑素后，这些微球进一步封装在海藻酸钠水凝胶中，形成用于皮肤再生的贴片。制备的贴片能够在早期募集交替激活（M2）巨噬细胞（IL-4 的快速释放）并在长期内促进血管生长（褪黑素的缓慢释放），从而显著增强皮肤再生。这些结果还表明，这种新型给药系统具有递送多种治疗药物和实现协同作用的潜力。
