Artificial pulmonary surfactant as a carrier for intratracheally instilled insulin
AbstractAim:The relative bioavailabilities and effects on lung injury alleviation of 4 insulin-artificial pulmonary surfactant (INS-APS) preparations were studied in normal rats. The relationship between the minimal surface tension (γmin) of INS-APS and the absorption of insulin was also investigated.Methods:Four formulations of APS [1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/lecithin/palmitic acid (PA), DPPC/1-hexadecanol (Hex)/tyloxapol (Tyl), DPPC/L-α-phosphatidyl-DL-glycerol sodium salt (PG), DPPC/Tyl] were prepared by thin-film sonication method and direct sonication. The γmin of 4 APS dispersions was examined with and without INS by pulsating with a bubble surface tensiometer. In vivo experiments were performed in which serum glucose change and the insulin level were measured by an enzymatic glucose reagent kit and a radioimmunology assay kit after IT to rats. The reduction in lung injury by INS-APS following 7 d of consecutive administration was evaluated by the pulmonary edema index (the weight ratio of wet lung to dry lung) and histopathology examination.Results:The γmin of all APS dispersions were below 10 mN/m. There was no significant difference (P> 0.05) between the γmin of APS and the corresponding INS-APS. In vivo experiments showed a significant glucose level decrease and insulin absorption increase (P<0.05) in the presence of APS, compared to the insulin solution alone. From the results, we found that the pulmonary edema index values of all the INS-APS groups were significant lower (P<0.05) than that of the insulin solution group, and there were no significant differences (P>0.05) between INS/DPPC/Tyl, INS/DPPC/PG, and the control group. The pulmonary edema indices and histopathological observation indicated that INS-APS could alleviate lung injury.Conclusion:The most potent hypoglycemic effect and insulin absorption increase in this study were obtained with INS/DPPC/Tyl. According to the results, there was a linear correlation between the γmin and relative bioavailability of INS-APS, suggesting a possible effect of the γmin of carriers on the in vivo absorption of insulin. APS, DPPC/Tyl, and DPPC/PG dispersions might be the most efficient insulin pulmonary delivery carriers in achieving a lower γmin, enhancing insulin absorption, and decreasing lung injury.