Biodegradable celastrol-loaded albumin nanoparticles ameliorate inflammation and lipid accumulation in diet-induced obese mice
Biodegradable celastrol-loaded albumin nanoparticles ameliorate inflammation and lipid accumulation in diet-induced obese mice
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可生物降解的负载白蛋白纳米颗粒的雷公藤红素可改善饮食诱导的肥胖小鼠的炎症和脂质积累。
DOI：
10.1039/d1bm01637g
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发表时间：
2021-12-24
影响因子：
6.6
通讯作者：
Rong, Jianhui
中科院分区：
文献类型：
--
作者：
Fan, Ni;Zhao, Jia;Rong, Jianhui
肥胖的特征是内质网（ER）应激，慢性炎症和代谢功能障碍。控制肥胖是预防非酒精性脂肪肝、糖尿病、心血管疾病和癌症的关键。雷公藤红素作为一种很有前途的减肥药物，其水溶性差，口服生物利用度低，在临床应用中面临挑战。本研究旨在开发一种生物相容的白蛋白基纳米粒载体系统，用于饮食诱导的肥胖小鼠中雷公藤红素的控制释放。将雷公藤红素负载到牛血清白蛋白（BSA）纳米粒中，通过高压均质化得到雷公藤红素-BSA-NPs。结果表明，制得的南蛇藤酚-BSA-纳米粒呈球形，粒径分布窄，平均粒径为125.6 ± 2.2 nm，载药量为13.88 ± 0.12%，在168 h内具有良好的缓释效果。与游离雷公藤红素相比，雷公藤红素-BSA-NPs有效地提高了细胞摄取、肠吸收和肝沉积。在动物实验中，雷公藤红素-BSA-NP在降低脂质积累、改善胰岛素敏感性和减少饮食诱导的肥胖症中的炎症方面优于游离雷公藤红素。总的来说，雷公藤红素-BSA-NP在治疗饮食诱导的肥胖症中表现出更好的生物利用度和体内功效。重要的是，这种基于白蛋白的纳米颗粒可以是用于控制释放疏水化合物（例如，雷公藤红素）用于治疗肥胖症和非酒精性脂肪性肝病。
Obesity is hallmarked by endoplasmic reticulum (ER) stress, chronic inflammation and metabolic dysfunctions. The control of obesity is the key to preventing the onset of non-alcoholic fatty liver disease, diabetes, cerebro-cardiovascular diseases and cancers. As a promising anti-obesity drug, plant-derived celastrol is challenged by poor water solubility and low oral bioavailability in clinical applications. The present study was designed to develop a biocompatible albumin-based nanoparticle carrier system for the controlled release of celastrol in diet-induced obese mice. Celastrol was loaded into bovine serum albumin (BSA) nanoparticles to yield celastrol-BSA-NPs by high pressure homogenization. Celastrol-BSA-NPs exhibited spherical morphology, narrow size distribution with a diameter of 125.6 ± 2.2 nm, satisfactory drug-loading efficiency at 13.88 ± 0.12% and a sustained-release profile over a period of 168 h. Compared with free celastrol, celastrol-BSA-NPs effectively improved cellular uptake, intestinal absorption and hepatic deposition. In animal experiments, celastrol-BSA-NPs outperformed free celastrol in lowering lipid accumulation, improving insulin sensitivity, and reducing inflammation in diet-induced obesity. Collectively, celastrol-BSA-NPs exhibited better bioavailability and in vivo efficacy in the treatment of diet-induced obesity. Importantly, such albumin-based nanoparticles may be a general biocompatible drug carrier system for the controlled release of hydrophobic compounds (e.g., celastrol) for the treatment of obesity and non-alcoholic fatty liver disease.