title: Novel hormonal delivery method using the ink-jet technology: application to pulmonary insulin therapies.
abstract: BACKGROUND
  A device developed based on ink-jet printer technology can precisely control the size and volume of droplets ejected. Here, we evaluated the application of this technology to the pulmonary administration of insulin mist as a therapeutic measure for diabetes.
  
  
  METHODS
  Insulin ejected from the ink-jet device was initially characterized by high-performance liquid chromatography (HPLC) and mass spectrometry. Its effects on D-glucose uptake rate by L6 cells were then investigated. Next, different insulin solutions (with or without additives or ink-jet processing) were subcutaneously administered, and their pharmacodynamic features were evaluated. Finally, decreases in plasma glucose level in rats were examined after ventilator-assisted pulmonary administration of insulin mist.
  
  
  RESULTS
  Neither the HPLC nor the mass spectrometry profile of insulin was altered by the ink-jet process. The D-glucose uptake rate by L6 cells that received the recovered aerosolized insulin solution was similar to that of cells treated with control insulin, at 107%. Neither the addition of additives nor the ink-jet process used for insulin aerosolization impaired the plasma glucose-lowering action of subcutaneously injected insulin. Similarly, the efficacy of pulmonary insulin administration was not affected by the additives or the ink-jet process. Plasma glucose levels showed a trend towards decreasing after ventilator-assisted pulmonary administration of insulin mist. Plasma insulin level increased 30 min after the inhalation.
  
  
  CONCLUSIONS
  The ink-jet process did not affect the quality or biological activity of insulin, suggesting the potential use of the ink-jet device for insulin inhalation therapy for diabetes.
authors.affiliation: Department of General Internal Medicine, Jikei University School of Medicine, Aoto Hospital, Tokyo, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Nemoto
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Hiki
authors.forename: Kousuke
authors.initials: K
authors.lastname: Shimada
authors.forename: Nozomu
authors.initials: N
authors.lastname: Nakai
authors.forename: Kei
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Sachiko
authors.initials: S
authors.lastname: Inoue
authors.forename: Naoko
authors.initials: N
authors.lastname: Sakurada
authors.forename: Hideki
authors.initials: H
authors.lastname: Kaneko
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugita
authors.forename: Masataka
authors.initials: M
authors.lastname: Okabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000042:Absorption; D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002460:Cell Line; D003408:Cresols / Q000737:chemistry; D004355:Drug Stability; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008297:Male; D009330:Nebulizers and Vaporizers; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012521:Sarcosine / Q000031:analogs & derivatives / Q000737:chemistry; D013678:Technology, Pharmaceutical
chemical_list: D000336:Aerosols; D001786:Blood Glucose; D003408:Cresols; D007004:Hypoglycemic Agents; D007328:Insulin; D014677:Pharmaceutical Vehicles; C031573:insulin, fluorescein-isothiocyanated-; C032538:4-cresol; C025231:sarkosyl; D001120:Arginine; D016650:Fluorescein-5-isothiocyanate; D012521:Sarcosine