Department of Rheumatology and Immunology, Institute of Translational Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Adv Healthc Mater. 2022 Sep;11(17):e2201105. doi: 10.1002/adhm.202201105. Epub 2022 Jun 30.
Mesenchymal stem cells derived exosomes (MSC-exos) exhibit an intrinsic and directed efficiency for multiple diseases, while their versatile and effective delivery to the target site is still a challenge. Herein, inspired by the acids and enzymes resistant property of sealing gelatin capsules, novel MSC-exo-encapsulated oral microcapsules are presented for colitis treatment. Based on a microfluidic electrospray technique, MSC-exos are first encapsulated in sodium alginate (SA) hydrogel microspheres with sustainable bioactivity. The resultant SA microspheres are then coated with a middle gelatin layer to protect MSC-exos from degradation. Especially, with an enteric coating-Eudragit FS30D on the outer layer, the resistance of the microcapsules in gastric juice is further enhanced. The prepared microcapsules maintain the stability and bioactivity of the MSC-exos during storage, protect them from the harsh conditions in the gastrointestinal tract, and enable the release of actives in the suitable sites for exerting their biological functions. In addition, these MSC-exos encapsulated microcapsules reduce the proinflammatory cytokines levels of inflammatory macrophages and impaired colonic epithelial cells, which exhibit superior damage repair ability in injured colon sites. Thus, it is believed that the proposed oral MSC-exos encapsulated microcapsules are valuable for many practically clinical treatments.
间充质干细胞衍生的外泌体 (MSC-exos) 对多种疾病具有内在的靶向治疗效率,但其向靶部位的多功能有效递送仍然是一个挑战。受密封明胶胶囊的耐酸耐酶特性的启发,本文提出了一种新型的用于结肠炎治疗的 MSC-exo 包封口服微胶囊。基于微流控电喷雾技术,首先将 MSC-exos 包封在具有可持续生物活性的海藻酸钠 (SA) 水凝胶微球中。然后,用中间明胶层涂覆所得的 SA 微球,以保护 MSC-exos 免受降解。特别是,通过外层肠溶包衣 Eudragit FS30D,进一步增强了微胶囊在胃液中的耐受力。所制备的微胶囊在储存过程中保持 MSC-exos 的稳定性和生物活性,保护它们免受胃肠道恶劣条件的影响,并使活性物质在合适的部位释放以发挥其生物学功能。此外,这些包封 MSC-exos 的微胶囊降低了炎症巨噬细胞和受损结肠上皮细胞的促炎细胞因子水平,在受损结肠部位表现出优异的损伤修复能力。因此,我们相信所提出的口服 MSC-exos 包封微胶囊在许多实际的临床治疗中具有价值。