Abstract
The limited therapeutic efficacy of oral medications against ulcerative colitis (UC) is attributed to inadequate drug exposure to inflammation site in the colon. To address this challenge, we developed a pH-triggered oral hydrogel microsphere system composed of alginate/silk fibroin (Alg/SF) using zinc ions (Zn2+) as a crosslink agent for colon-targeted delivery. This system, with moderate gelation toughness, can protect the anti-inflammatory drug bornyl acetate (BA) from gastric degradation, ensuring its delivery to the colon. SF effectively shields the microspheres during passage through the small intestine and then facilitates rapid drug release upon reaching the colon. We evaluated the efficacy of this strategy in murine models of both acute and chronic colitis, demonstrating its significant capacity to attenuate pro-inflammatory cytokine secretion, enhance intestinal barrier restitution, and modulate immune cell responses for effective amelioration of colitis-associated symptoms. Upon oral administration of microspheres, their therapeutic efficacy against both acute and chronic UC is demonstrated to be superior to that of a widely used clinical drug, 5-aminosalicylic acid. Overall, the oral hydrogel microspheres offer a promising approach to enhance the therapeutic outcomes of small molecule drug against UC.
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