Glucose-lowering effects of insulin delivered by oral inhalation in normal rats / 中国组织工程研究

ABSTRACT

BACKGROUND:Insulin taken orally is easy to be degraded by hydrochloric acid in the gastric juice and various enzymes in the gastrointestinal tract.It is hard for oral insulin to pass through the epithelial cell membrane in the gastrointestinal tract.Insulin delivered by injection needs at least 36 hours every administration.Many pulmonary administrations of insulin have been recentl studied,such as dry powder inhalation,aerosol inhalation,electron spraying,insulin nanometer technique,and absorption enhancer,with promising clinical application prospects.OBJECTIVE:To investigate the glucose-lowering effects of insulin delivered by oral inhalation in normal rats.METHODS:Thirty healthy male rats,weighing (220±30) g were randomly divided into seven groups:low dose insulin (1.0 U/kg,n=4),middle dose insulin (5.0 U/kg,n=4),high dose insulin (10,0 U/kg,n=4),insulin (2.0 U/kg) +5% lecithin (n=5),insulin (2.0 U/kg)+1% oleic acid (n=5),insulin (2.0 U/kg) +1% diethylenetriaminepentaacetic acid (DTPA; n=5),and blank control (n=3).At 0,30,60,120,180,240 minutes after administration.1.5μL blood was taken from rat tails through the use of ONE TOUCH~(TM) BASICTM PLUS blood glucose detection system for determination of blood glucose level and calculation of insulin pharmacological bioavailability under various conditions.RESULTS AND CONCLUSION:Insulin (1U/kg) markedly decreased glucose levels immediately after inhalation.Blood glucose level decreased with increasing insulin dose.Insulin (10 U/kg) could produce a 14.5% decrease of blood glucose level.Insulin (1 U/kg) could yield a pharmacological bioavailability of 11.5% in the absence of absorption enhancer.The concomitant administration of oleic acid,DTPA and lecithin appeared to be more effective in enhancing the pulmonary absorption of insulin,and decreasing blood glucose level.