Long Tao, Tan Weiwei, Tian Xiangmin, Tang Zongjian, Hu Keming, Ge Liming, Mu Changdao, Li Xinying, Xu Yongbin, Zhao Lei, Li Defu
Department of Pharmaceutics and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
College of Chemistry and Environment Protection Engineering, Southwest Minzu University, Chengdu 610041, Sichuan, China.
Int J Biol Macromol. 2023 Jan 31;226:485-495. doi: 10.1016/j.ijbiomac.2022.12.040. Epub 2022 Dec 12.
Microsphere with sphere-in-capsule structure is a multi-drugs delivery system to achieve the purpose of combination therapy. In this paper, we have prepared gelatin/alginate-based microspheres with sphere-in-capsule structure by a relatively fast, simple, and easily large-scale industrialized emulsification method for spatiotemporal manipulative drug release in gastrointestinal tract. Calcium alginate microspheres encapsulated with bovine serum albumin (BSA) were first prepared as inner microspheres, and then inner microspheres and ranitidine hydrochloride (RH) were co-encapsulated by gelatin microspheres to form double-layer microspheres with sphere-in-capsule structure. The size and distribution of microspheres can be easily controlled by emulsifying conditions. The microspheres with sphere-in-capsule structure displayed desirable encapsulation efficiency of BSA (61.52 %) and RH (56.07 %). The in vitro simulated drug release showed the spatiotemporal release feature of microspheres with sphere-in-capsule structure. In the specific simulated fluid, the release behavior and cumulative release of RH (sustainedly released 95 % in simulated gastric fluid) and BSA (rapidly released 73 % in simulated intestinal fluid) were different. The drug release mechanisms were analyzed to determine RH and BSA's release behavior. Overall, the microspheres with sphere-in-capsule structure have the potential application of spatiotemporal manipulative drug delivery in the gastrointestinal tract.
具有胶囊内球结构的微球是一种用于实现联合治疗目的的多药物递送系统。在本文中，我们通过一种相对快速、简单且易于大规模工业化的乳化方法，制备了具有胶囊内球结构的明胶/海藻酸盐基微球，用于在胃肠道中进行时空操纵性药物释放。首先制备包裹有牛血清白蛋白（BSA）的海藻酸钙微球作为内微球，然后将内微球与盐酸雷尼替丁（RH）共同包裹在明胶微球中，形成具有胶囊内球结构的双层微球。微球的尺寸和分布可通过乳化条件轻松控制。具有胶囊内球结构的微球对BSA（61.52%）和RH（56.07%）显示出理想的包封效率。体外模拟药物释放显示了具有胶囊内球结构的微球的时空释放特性。在特定的模拟流体中，RH（在模拟胃液中持续释放95%）和BSA（在模拟肠液中快速释放73%）的释放行为和累积释放情况不同。对药物释放机制进行了分析，以确定RH和BSA的释放行为。总体而言，具有胶囊内球结构的微球在胃肠道中具有时空操纵性药物递送的潜在应用。
