Adipose Tissue‐Targeted Delivery of Rosiglitazone With Iron Oxide Nanoparticles Ameliorates Insulin Resistance in Male Mice

OBJECTIVE: This study aimed to assess iron oxide magnetic nanoparticles (MNPs) for adipose tissue-targeted therapeutics to restore adipose tissue function and insulin sensitivity in obesity. METHODS: The insulin-sensitizing effects of rosiglitazone and known adverse effects were leveraged for this proof-of-concept assessment of adipose tissue drug targeting. Rosiglitazone was adsorbed to alendronic acid-coated MNPs (rosiMNPs) and a biocompatible magnet implanted in the right inguinal white adipose tissue (ingWAT) of obese, insulin resistant male mice. Following rosiMNP treatment (1.5 mg/kg/day, 18 days), insulin sensitivity and adipose tissue health were assessed. RESULTS: RosiMNPs restored insulin sensitivity as well as systemic rosiglitazone (1.5 mg/kg/day, 18 days), with a shift in adipocyte size compatible with PPARγ-induced adipocyte hyperplasia and no increase in circulating adiponectin. PPARγ target genes were induced in ingWAT with rosiMNPs or systemic rosiglitazone, but only in liver and gonadal WAT of systemically treated mice. Additionally, iron accumulation was shown in the right, targeted ingWAT depot, but not in the left, untargeted ingWAT, kidney, or liver, suggesting targeting was achieved. Unfortunately, the dose and duration of systemic treatment were ineffective at inducing changes in kidney. CONCLUSIONS: Results demonstrate the potential benefits of adipose tissue-targeted therapeutics to improve adipose tissue function to restore insulin sensitivity to prevent the metabolic complications of obesity.