Xie Yixuan, Shao Ruomei, Lin Yali, Wang Chunnan, Tan Ying, Xie Weidong, Sun Shuqing
Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
Department of Biomedical Engineering, Tsinghua University, Beijing 100084, China.
Pharmaceutics. 2021 Jun 2;13(6):827. doi: 10.3390/pharmaceutics13060827.
In this paper, we prepared patches that were composed of a degradable microneedle (MN) array with a soft backing provided for the skin tissue. We then performed a transdermal delivery of anti-obesity drugs to evaluate the effectiveness of β3 adrenergic receptor CL316243 in obesity treatment in overweight mice induced by a high-fat diet. Eighty male National Institutes of Health (NIH) mice were randomly divided into four obese groups or the control group. The obesity groups were given a high-fat diet for 15-18 weeks to establish an obese model. Afterward, the obese groups were divided into the following four groups: the control group, the unloaded MN group, the CL-316243 MN group, and the injection group. For the injection group, the group of mice was injected subcutaneously with CL316243 (1 mg/(kg·day)) for 15 days. Furthermore, the CL-316243 MN group was given a lower dose (0.1 mg/(kg·day)) for 15 days. After weighing the mice, we used Western blotting to detect the expression of uncoupling protein 1 (UCP1) in the adipose tissue around the mouse viscera. The results stated that the weight of the CL-316243 MN group and the injection group dropped, and the UCP1 protein expression of brown adipose tissue (BAT) significantly increased. The results demonstrated the β3 adrenergic receptor agonist CL316243 could be carried into the body through MN, and the dose applied was considerably smaller than the injection dose. The reason for this may arise from the CL-316243 being delivered by MN arrays to subcutaneous adipose tissue more efficiently, with an even distribution, compared to that of the injection dose. This technique provides a new and feasible way to treat obesity more effectively.
在本文中,我们制备了由可降解微针(MN)阵列和为皮肤组织提供的柔软背衬组成的贴片。然后,我们进行了抗肥胖药物的透皮给药,以评估β3肾上腺素能受体CL316243在高脂饮食诱导的超重小鼠肥胖治疗中的有效性。80只雄性美国国立卫生研究院(NIH)小鼠被随机分为四个肥胖组或对照组。肥胖组给予高脂饮食15 - 18周以建立肥胖模型。之后,肥胖组被分为以下四组:对照组、未负载微针组、CL - 316243微针组和注射组。对于注射组,小鼠皮下注射CL316243(1毫克/(千克·天)),持续15天。此外,CL - 316243微针组给予较低剂量(0.1毫克/(千克·天)),持续15天。对小鼠称重后,我们使用蛋白质免疫印迹法检测小鼠内脏周围脂肪组织中解偶联蛋白1(UCP1)的表达。结果表明,CL - 316243微针组和注射组的体重下降,棕色脂肪组织(BAT)的UCP1蛋白表达显著增加。结果表明,β3肾上腺素能受体激动剂CL316243可通过微针携带进入体内,且应用剂量远小于注射剂量。其原因可能是与注射剂量相比,CL - 316243通过微针阵列更有效地递送至皮下脂肪组织,且分布均匀。该技术为更有效地治疗肥胖提供了一种新的可行方法。