Colon-Targeted Oral Delivery of Hydroxyethyl Starch-Curcumin Microcapsules Loaded with Multiple Drugs Alleviate DSS-Induced Ulcerative Colitis in Mice.

Combination therapy through colon-targeted oral delivery of multiple drugs presents a promising approach for effectively treating ulcerative colitis (UC). However, the co-delivery of drugs with diverse physicochemical properties in a single formulation remains a formidable challenge. In this study, we designed microcapsules based on hydroxyethyl starch-curcumin conjugates to enable the simultaneous delivery of hydrophobic dexamethasone acetate (DA) and hydrophilic cefazolin sodium (CS), yielding multiple drug-loaded microcapsules (CDHC-MCs) tailored for colon-targeted therapy of UC. Thorough characterization confirmed the successful synthesis and exceptional biocompatibility of CDHC-MCs. Biodistribution studies demonstrated that the microcapsules exhibited an impressive inflammatory targeting effect, accumulating preferentially in inflamed colons. In vivo experiments employing a dextran sulfate sodium (DSS)-induced UC mouse model revealed that CDHC-MCs not only arrested UC progression but also facilitated the restoration of colon length and alleviated inflammation-related splenomegaly. These findings highlight the potential of colon-targeted delivery of multiple drugs within a single formulation as a promising strategy to enhance UC treatment, and the CDHC-MCs developed in this study hold great potential in developing novel oral formulations for advanced UC therapy. This article is protected by copyright. All rights reserved.