Cheng Qikun, Liu Lu, Xie Mingzhi, Li Hang, Ma Dong, Xue Wei
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China.
Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, 510515, China.
Adv Healthc Mater. 2021 Apr;10(8):e2001953. doi: 10.1002/adhm.202001953. Epub 2021 Jan 14.
Probiotics are closely related to human health. However, it is hard to find an appropriate disintegration mode for encapsulation to balance the survival, release, and adhesion of probiotics simultaneously during the current colon-targeted oral delivery, which leads to limited colonization. In this study, an enzyme-triggered fuse-like microcapsule is constructed using alginate and protamine via the electrostatic droplet combined with the layer by layer self-assembly. The multilayer microcapsule can protect the probiotics in the stomach and disintegrate layer by layer under the catalysis of trypsin in the intestine. The formulation with two protamine layers showed the best protection for Escherichia coli MG1655 (EM) during the oral delivery; as well the minimal release at the gastric pH value but a burst release after 1 h at the intestinal pH value. In particular, the adhesion strength of EM is improved with the increase of the layer number. In vivo experiments demonstrate that the EM enters into the stationary phase within 12 h in the colon. Moreover, the blood biochemistry and histological analysis demonstrates the safety of the microcapsule formulation. It can be concluded that this microcapsule can help the probiotics survive during the delivery, then release and colonize in the colon.
益生菌与人类健康密切相关。然而，在当前的结肠靶向口服给药过程中，很难找到一种合适的包封崩解模式来同时平衡益生菌的存活、释放和黏附，这导致其在结肠的定植受限。在本研究中，通过静电滴注结合层层自组装技术，利用海藻酸盐和鱼精蛋白构建了一种酶触发的类熔断微胶囊。多层微胶囊可以在胃中保护益生菌，并在肠道中胰蛋白酶的催化下逐层崩解。含有两层鱼精蛋白的制剂在口服给药过程中对大肠杆菌MG1655（EM）表现出最佳的保护作用；在胃pH值下释放量最小，但在肠道pH值下1小时后出现突释。特别是，EM的黏附强度随着层数的增加而提高。体内实验表明，EM在结肠中12小时内进入稳定期。此外，血液生化和组织学分析证明了微胶囊制剂的安全性。可以得出结论，这种微胶囊可以帮助益生菌在递送过程中存活，然后在结肠中释放并定植。
