Pulmonary absorption of insulin mediated by tetradecyl-beta-maltoside and dimethyl-beta-cyclodextrin.
OBJECTIVE
To determine if tetradecyl-beta-maltoside (TDM) and dimethyl-beta-cyclodextrin (DMbetaCD) enhance pulmonary absorption of insulin and to investigate if they do so by a reversible action on respiratory epithelium.


METHODS
Insulin formulated with saline, TDM, or DMbetaCD was administered intratracheally, after laryngoscopic visualization, as a spray to anesthetized rats. Reversibility studies were conducted in intact rats by administering insulin at different time points after administration of TDM or DMbetaCD. The pharmacodynamics and pharmacokinetics of insulin formulations were assessed by measuring plasma glucose and plasma insulin concentrations.


RESULTS
When insulin formulated with increasing concentrations (0.06-0.25%) of TDM or DMbetaCD were administered to anesthetized rats, there was a concentration-dependent decrease in plasma glucose and increase in plasma insulin concentrations. The relative bioavailability of insulin formulations containing TDM was higher (0.34-0.84%) than that of formulations containing DMbetaCD (0.19-0.48%). When insulin was administered 120 min after an agent was administered, in the reversibility study, no significant change in plasma glucose and insulin levels occurred compared to control.


CONCLUSIONS
Both TDM and DMBCD enhance pulmonary absorption of insulin, with TDM being more efficacious than DMbetaCD in enhancing insulin absorption via pulmonary administration. The effects of TDM and DMbetaCD on respiratory epithelium are reversible, and the epithelium reestablishes its normal physiologic barrier 120 min after exposure to these agents.
Hussain
Alamdar
A
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Drive, Amarillo, Texas 79106, USA.
Yang
Tianzhi
T
Zaghloul
Abdel-Azim
AA
Ahsan
Fakhrul
F
D000042:Absorption; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects; D003505:Cyclodextrins / Q000494:pharmacology*; D007322:Instillation, Drug; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008320:Maltose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000378:metabolism; D013997:Time Factors; D014132:Trachea; D047392:beta-Cyclodextrins
D000277:Adjuvants, Pharmaceutic; D001786:Blood Glucose; D003505:Cyclodextrins; D007328:Insulin; D047392:beta-Cyclodextrins; C459187:tetradecyl maltoside; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D008320:Maltose