Intervention effects of delivery vehicles on the therapeutic efficacy of 6-gingerol on colitis
2022
Tian, Wenni | Wang, Haonan | Zhu, Ying | Wang, Qun | Song, Mingyue | Cao, Yong | Xiao, Jie
The emerging concept that “the maximized therapeutic efficacy of encapsulates would be achieved by inducing appropriate absorption site and pharmacological signal pathways through smart intervention of targeted delivery systems” is quite intriguing in the field of drug delivery. Herein, we developed 6-gingerol (6G) loaded delivery system in the form of nanostructured lipid carriers (6G-NLC) or NLC imbedded microcapsule (6G-MC). The modulation effects of the constructed formulations on the digestive fate and functioning mechanisms of 6-gingerol on colitis were investigated. The small intestine dominant absorption of 6G-NLC differed significantly with the colorectal dominated accumulation of 6G-MC in terms of the site-specific release behavior, biodistribution and transit time. Moreover, 6G-NLC alleviated DSS-induced colitis primarily through interfering with the antioxidant/anti-inflammatory pathways and Firmicutes/Bacteroidetes ratio. Whereas, better therapeutic efficacy was achieved in 6G-MC via sustained release at site close to the colonic lesion, and triggering multiple mitigation mechanisms including enhancing the mucus barrier and immune homeostasis, maintaining the structure and diversity of gut microbiota and promoting the intestinal barrier function. This work confirmed that rational design of oral delivery system can flexibly interfere with the pharmacological function pathways of encapsulated cargos, guided by which the maximized and precise therapeutic efficacy could be achieved.
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