title: Selective adipose tissue ablation by localized, sustained drug delivery.
abstract: The reduction of adipose depots is widely considered to be the optimal approach to limit pathologies associated with obesity. While many current antiobesity strategies are centered on regulating satiety, these approaches typically attempt an overall weight loss and are unable to target distinct adipose depots specifically associated with disease risk. The authors report a novel therapeutic modality utilizing localized and sustained delivery of drugs to provide for the selective ablation of adipose tissue. Using the epididymal fat pad of Sprague-Dawley rats as a model, they injected into the tissue poly(lactide-co-glycolide) microspheres encapsulating tumor necrosis factor-alpha, a well-known regulator of adipose tissue mass. The utility of this approach was investigated in vivo by measuring the fat pad mass relative to the contralateral control within the same animal (n = 4 at each time point) and in vitro by measuring apoptosis in adipose organ cultures. The authors demonstrated control over the localization of tumor necrosis factor-alpha by performing blood analysis. This is the first report of localized drug delivery for adipose tissue ablation, and these results indicate the potential utility of the general tissue ablation approach for treatment of numerous pathologies.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor 48109, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Richardson
authors.forename: William L
authors.initials: WL
authors.lastname: Murphy
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000473:pathology; D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis; D001673:Biodegradation, Environmental; D001786:Blood Glucose / Q000032:analysis; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D006016:Glycolates; D007267:Injections; D007328:Insulin / Q000097:blood; D019344:Lactic Acid; D008297:Male; D008863:Microspheres; D009765:Obesity / Q000628:therapy*; D009924:Organ Culture Techniques; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D006016:Glycolates; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid