title: An in vivo experiment to improve pulmonary absorption of insulin using microbubbles.
abstract: BACKGROUND
  Gas-filled phospholipid-based ultrasonic microbubbles (PUMs) are widely used in diagnostic imaging. The micro- or nanoparticle size and the physiochemical nature of shell provide the potential for a new way to improve pulmonary absorption for peptides and proteins.
  
  
  METHODS
  Male Sprague-Dawley rats were fasted for 12 h. Then insulin solution and insulin-PUM mixture solution were administered by intratracheal instillation. The hypoglycemic effect was observed to evaluate insulin absorption after lung administration. Fluorescein isothiocyanate-dextran (molecular mass, 4 kDa) was used as the index of evaluating drug alveolar deposition and absorption by visualization techniques.
  
  
  RESULTS
  Administration of insulin solution containing PUMs significantly reduced the blood glucose levels of Sprague-Dawley rats, compared with administration of insulin-only solution. The minimum reductions of the blood glucose concentration produced by insulin solution containing PUMs and by an insulin-only solution reached 60.81% and 34.60% of the initial glucose levels, respectively, and their bioavailabilities relative to subcutaneous injection were 48.58% and 29.09%, respectively. Histopathological study of the lung showed no changes in the morphology of the pulmonary alveoli after administration to these drugs. Only a slight inflammatory cell infiltration in the alveoli could be found in some rats.
  
  
  CONCLUSIONS
  These results suggested that PUMs might be used as an effective way to improve pulmonary absorption for peptides and proteins.
authors: Wenzhou Medical College, Wenzhou, Zhejiang Province, China.
authors: Ying-Zheng
authors: YZ
authors: Zhao
authors: Yan-Yan
authors: YY
authors: Xu
authors: Xing
authors: X
authors: Li
authors: Cui-Tao
authors: CT
authors: Lu
authors: Lu
authors: L
authors: Zhang
authors: Dan-Dan
authors: DD
authors: Dai
authors: Chang-Zheng
authors: CZ
authors: Sun
authors: Hai-Feng
authors: HF
authors: Lv
authors: Xiao-Kun
authors: XK
authors: Li
authors: Wei
authors: W
authors: Yang
mesh_terms: D000042:Absorption; D000280:Administration, Inhalation; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism*; D006651:Histocytochemistry; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D045423:Microbubbles; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007328:Insulin