title: Evaluation of novel particles as an inhalation system for GLP-1.
abstract: OBJECTIVE
  The feasibility of administering native glucagon-like peptide 1 (GLP-1) as GLP-1 Technosphere Inhalation Powder for diabetes therapy has been demonstrated in a rat model.
  
  
  METHODS
  GLP-1 Technosphere Inhalation Powders containing 5, 10 and 15% GLP-1 were prepared and administered to healthy female Sprague-Dawley rats and to male Zucker diabetic obese rats. Rats received a single dose of GLP-1 Technosphere Powder by pulmonary insufflation. GLP-1 pharmacokinetic and pharmacodynamic responses were measured.
  
  
  RESULTS
  Maximum circulating GLP-1 concentrations were achieved at approximately 10 min after dosing with detectable levels at 40 min. In a food consumption study, Sprague-Dawley rats receiving GLP-1 Technosphere Powder once-daily consumed less food than control rats for up to 24 h after dosing. Cumulative food consumption was decreased approximately 10% after 78 h. In an intraperitoneal glucose tolerance test, Zucker diabetic fatty rats receiving 2 mg GLP-1 Technosphere Powder (0.3 mg GLP-1) by pulmonary insufflation exhibited lower glucose concentrations and higher insulin concentrations than control rats. Pancreatic evaluations showed no differences in apoptotic index or cell proliferation of beta-cells. In addition, a dose-related increase in insulin expression within the pancreas was observed.
  
  
  CONCLUSIONS
  These data demonstrate the feasibility of administering native GLP-1 as GLP-1 Technosphere Inhalation Powder for diabetes therapy.
authors.affiliation: MannKind Corporation, Valencia, CA, USA. aleone-bay@mannkindcorp.com
authors.forename: A
authors.initials: A
authors.lastname: Leone-Bay
authors.forename: M
authors.initials: M
authors.lastname: Grant
authors.forename: S
authors.initials: S
authors.lastname: Greene
authors.forename: G
authors.initials: G
authors.lastname: Stowell
authors.forename: S
authors.initials: S
authors.lastname: Daniels
authors.forename: A
authors.initials: A
authors.lastname: Smithson
authors.forename: S
authors.initials: S
authors.lastname: Villanueva
authors.forename: S
authors.initials: S
authors.lastname: Cope
authors.forename: K
authors.initials: K
authors.lastname: Carrera
authors.forename: S
authors.initials: S
authors.lastname: Reyes
authors.forename: P
authors.initials: P
authors.lastname: Richardson
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010446:Peptide Fragments; D052216:Glucagon-Like Peptide 1