2025-02-10 作者：ws 来源：文献：Celastrol-loaded PEG-PCL nanomicelles ameliorate inflammation, lipid accumulation, insulin resistance and gastrointestinal injury in diet-induced obese mice
文献链接：https://www.sciencedirect.com/science/article/abs/pii/S0168365919305103
作者：Jia Zhaoa,, Dan Luoa,, Zhong Zhang, Ni Fan, Yu Wang, Hong Nie, Jianhui Rong
原文摘要：
Botanical triterpene celastrol is a candidate drug for the treatment of obesity, except for concerns over the safety in clinical application. The present study was designed to investigate the anti-obesity, anti-inflammatory and toxic activities of celastrol-loaded nanomicelles (nano-celastrol) in diet-induced obese mice. Celastrol was loaded into PEG-PCL nanoparticles, yielding nano-celastrol with optimal size, spherical morphology, good bioavailability, slower peak time and clearance in mice. Nano-celastrol (5 or 7.5 mg/kg/d of celastrol) was administered into diet-induced obese C57BL/6 N male mice for 3 weeks. As result, higher dose nano-celastrol reduced body weight and body fat mass in an equally effective manner as regular celastrol, although lower dose nano-celastrol showed less activity. Similarly, nano-celastrol improved glucose tolerance in mice equally well as regular celastrol, whereas higher dose nano-celastrol improved the response to insulin. As for macrophage M1/M2 polarization in liver, nano-celastrol reduced the expression of macrophage M1 biomarkers (e.g., IL-6, IL-1β,TNF-α, iNOS) in a dose-dependent manner and marginally increased the expression of macrophage M2 biomarkers (e.g., Arg-1, IL-10). Moreover, celastrol could cause anus irritation and disturb intestinal and colonic integrity, whereas nano-celastrol did not cause any injury to mice. Collectively, nano-celastrol represents a translatable therapeutic opportunity for treating diet-induced obesity in humans.
mPEG - PCL 是一种嵌段共聚物，由甲氧基聚乙二醇（mPEG）和聚己内酯（PCL）两个嵌段组成。聚乙二醇单甲醚链段一端是甲氧基，另一端与聚己内酯链段相连。聚己内酯是一种由己内酯单体通过开环聚合形成的聚酯。这种嵌段共聚物结合了聚乙二醇的良好水溶性和聚己内酯的可生物降解性等特性。基于mPEG-PCL的性能，该文献制成的纳米纤维颗粒流程如下：
图：合成流程
纳米纤维颗粒的制备：
将mPEG-PCL共聚物和天酚溶解在氯仿中。然后通过注射器将溶液滴入蒸馏水中，在室温磁力搅拌器下温和搅拌，使PEG-PCL共聚物自组装成聚合体。得到的胶束离心，在低温、一定压强下冻干，得到最终干燥的纳米纤维颗粒。
图：电镜图像
结论：
该文献成功制备了基于mPEG-PCL合成的纳米纤维颗粒。结果表明，高剂量纳米纤维颗粒与常规纳米纤维颗粒同样有效地降低体重和体脂质量，而低剂量纳米纤维颗粒的活性较低。同样，纳米纤维颗粒与常规纤维颗粒一样改善了小鼠的糖耐量，而高剂量的纳米纤维颗粒改善了对胰岛素的反应。
