Abbasi Mehrnaz, Fan Zhaoyang, Dawson John A, Wang Shu
Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas 79409, USA.
College of Human Sciences, Auburn University, Auburn, AL, 36830, USA.
J Drug Deliv Sci Technol. 2024 Jan;91. doi: 10.1016/j.jddst.2023.105110. Epub 2023 Nov 15.
Obesity is a severe public health problem. Healthy lifestyle interventions are commonly recommended for fighting obesity. But they are hard to follow and have low efficacy. Pharmacotherapy and surgery are of high efficacy but are beset with side effects. Browning subcutaneous white adipose tissue (WAT) is a practical and efficient approach for combating obesity. Metformin, a commonly used FDA-approved antidiabetic drug, is potent to induce browning of WAT through phosphorylation and activation of AMP-activated protein kinase. However, oral administration of metformin has low oral bioavailability, fast renal clearance, and low target specificity that limit metformin's application in browning WAT. Local and transdermal delivery of metformin directly to subcutaneous WAT using injection or microneedle (MN) in combination with iontophoresis (INT) may solve these problems. In this paper, we administered metformin to C57BL/6J obese mice using the following three routes: transdermal delivery (MN and INT), local injection into inguinal WAT (IgWAT, a type of subcutaneous WAT in mice), and oral gavage. The anti-obesity and metabolic effects of metformin via these delivery routes were determined and compared. As compared to local IgWAT injection and oral gavage delivery, transdermal delivery of metformin using MN and INT resulted in 9% lower body weight and 7% decrease in body fat% accompanied by improved energy metabolism and decreased inflammation through browning IgWAT in obese C57BL/6J mice. Transdermal delivery of metformin using MN and INT is an effective approach in browning subcutaneous WAT for combating obesity and improving metabolic health.
肥胖是一个严重的公共卫生问题。健康的生活方式干预通常被推荐用于对抗肥胖。但它们难以遵循且效果不佳。药物治疗和手术虽效果显著但存在副作用。使皮下白色脂肪组织（WAT）褐色化是对抗肥胖的一种切实有效的方法。二甲双胍是一种经美国食品药品监督管理局（FDA）批准的常用抗糖尿病药物，它能够通过磷酸化和激活腺苷酸活化蛋白激酶来有效诱导WAT褐色化。然而，二甲双胍口服时口服生物利用度低、肾脏清除快且靶标特异性低，这些因素限制了二甲双胍在使WAT褐色化方面的应用。使用注射或微针（MN）结合离子电渗疗法（INT）将二甲双胍直接局部和经皮递送至皮下WAT或许可以解决这些问题。在本文中，我们通过以下三种途径给C57BL/6J肥胖小鼠施用二甲双胍：经皮递送（MN和INT）、局部注射到腹股沟WAT（IgWAT，小鼠皮下WAT的一种类型）以及口服灌胃。我们测定并比较了通过这些递送途径施用二甲双胍后的抗肥胖和代谢效应。与局部IgWAT注射和口服灌胃递送相比，使用MN和INT经皮递送二甲双胍可使肥胖的C57BL/6J小鼠体重降低9%，体脂百分比降低7%，同时通过使IgWAT褐色化改善能量代谢并减轻炎症。使用MN和INT经皮递送二甲双胍是使皮下WAT褐色化以对抗肥胖和改善代谢健康的一种有效方法。
