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Celastrol-conjugated carboxylmethyl chitosan for oral treatment of diet-induced obesity

Qikang Tian,Qianqian Han,Xin Zhu,Lan Zhang,Kun Chen,Zhishen Xie,Pan Wang,Xiangxiang Wu,Zhenqiang Zhang,Huahui Zeng

Celastrol is a promising drug candidate for treating diet-induced obesity, but the cytotoxicity and poor water solubility limit its clinical application. We prepared a novel celastrol conjugate (Cel-CMCS) with excellent water solubility (33.94 mg/mL), and then investigated its anti-obesity and toxic activities in diet-induced obese mice. Just as the parent celastrol, Cel-CMCS reduced body weight and body fat mass in an equally effective manner, but with lower toxicity. Collectively, Cel-CMCS provides a possible solution for the treatment of obesity in humans. In addition, the present study provided a practical experience of the development of carboxymethyl chitosan-based delivery system for poorly water-soluble drugs.