title: Characterization of alendronic- and undecylenic acid coated magnetic nanoparticles for the targeted delivery of rosiglitazone to subcutaneous adipose tissue.
abstract: Obesity is a state of positive energy balance where excess white adipose tissue accumulates to the detriment of metabolic health. Improving adipocyte function with systemic administration of thiazolidinediones (TZDs) improves metabolic outcomes in obesity, however TZD use is limited clinically due to undesirable side effects. Here we evaluate magnetic nanoparticles (MNPs) as a tool to target rosiglitazone (Rosi) specifically to adipose tissue. Results show Rosi can be adsorbed to MNPs (Rosi-MNPs) with hydrophobic coatings for which we present binding and release kinetics. Rosi adsorbed to MNPs retained the ability to induce PPARγ target gene expression in cells. Biodistribution analysis of radiolabeled Rosi-MNPs revealed a fat-implanted magnet significantly enhanced localization of Rosi to the targeted adipose tissue when administered by subcutaneous injection to obese mice. We propose MNPs for targeted delivery of anti-diabetic agents to superficially located subcutaneous adipose tissue.
authors: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
authors: Katayoun
authors: K
authors: Saatchi
authors: Northern Medical Program, University of Northern British Columbia, Prince George, BC, Canada.
authors: Sarah E
authors: SE
authors: Tod
authors: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
authors: Donna
authors: D
authors: Leung
authors: Northern Medical Program, University of Northern British Columbia, Prince George, BC, Canada.
authors: Kenton E
authors: KE
authors: Nicholson
authors: Instituto de Ciencia de Materiales de Aragón (ICMA), CSIC-Universidad de Zaragoza, Zaragoza, Spain.
authors: Irene
authors: I
authors: Andreu
authors: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
authors: Christian
authors: C
authors: Buchwalder
authors: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
authors: Veronika
authors: V
authors: Schmitt
authors: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada. Electronic address: urs.hafeli@ubc.ca.
authors: Urs O
authors: UO
authors: Häfeli
authors: Northern Medical Program, University of Northern British Columbia, Prince George, BC, Canada. Electronic address: sarah.gray@unbc.ca.
authors: Sarah L
authors: SL
authors: Gray
mesh_terms: D000273:Adipose Tissue; D000818:Animals; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D058185:Magnetite Nanoparticles; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy; D000077154:Rosiglitazone; D050151:Subcutaneous Fat; D045162:Thiazolidinediones / Q000008:administration & dosage*; D014018:Tissue Distribution; D014476:Undecylenic Acids
chemical_list: D007004:Hypoglycemic Agents; D058185:Magnetite Nanoparticles; D045162:Thiazolidinediones; D014476:Undecylenic Acids; D000077154:Rosiglitazone
keywords: Adipose tissue; Drug targeting; Magnetic nanoparticles; Obesity; PPARγ; Type 2 diabetes