Anti-obesity and metabolic benefits of metformin: Comparison of different delivery routes

Mehrnaz Abbasi, Zhaoyang Fan, John A. Dawson, Shu Wang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number105110
JournalJournal of Drug Delivery Science and Technology
Volume91
DOIs
StatePublished - Jan 2024

Keywords

  • Adipose tissue browning
  • Iontophoresis
  • Metformin
  • Microneedle
  • Obesity
  • Targeted delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

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