Gelatin/alginate-based microspheres with sphere-in-capsule structure for spatiotemporal manipulative drug release in gastrointestinal tract

Microsphere with sphere-in-capsule structure is a multi-drugs delivery system to achieve the purpose of com-bination 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 spatiotem-poral 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 ra-nitidine 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 emulsi-fying 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.

Automated summary

In this paper, gelatin/alginate-based microspheres with sphere-in-capsule structure were prepared using a fast and easy emulsification method. The microspheres can release drugs spatiotemporally in the gastrointestinal tract. The size and distribution of the microspheres can be controlled by emulsification conditions. The microspheres showed good encapsulation efficiency for both BSA and RH. In vitro simulated drug release demonstrated the spatiotemporal release feature of the microspheres. The release behavior and cumulative release of RH and BSA in different simulated fluids were analyzed. The microspheres have the potential for manipulative drug delivery in the gastrointestinal tract.