Artificial pulmonary surfactant as a carrier for intratracheally instilled insulin

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:JK0803zhaozhenhong
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Aim:The relative bioavailabilities and effects on lung injury alleviation of 4 insu-lin-artificial pulmonary surfactant (INS-APS) preparations were studied in normalrats.The relationship between the minimal surface tension (γ_(min)) of INS-APS andthe absorption of insulin was also investigated.Methods:Four formulations ofAPS[1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/lecithin/palmitic acid(PA),DPPC/1-hexadecanol (Hex)/tyloxapol (Tyl),DPPC/L-α-phosphatidyl-DL-glyc-erol sodium salt (PG),DPPC/Tyl]were prepared by thin-film sonication methodand direct sonication.The γ_(min) of 4 APS dispersions was examined with andwithout INS by pulsating with a bubble surface tensiometer.In vivo experimentswere performed in which serum glucose change and the insulin level were mea-sured by an enzymatic glucose reagent kit and a radioimmunology assay kit afterIT to rats.The reduction in lung injury by INS-APS following 7 d of consecutiveadministration was evaluated by the pulmonary edema index (the weight ratio ofwet lung to dry lung) and histopathology examination.Results:The γ_(min) of allAPS dispersions were below 10 mN/m.There was no significant difference (P>0.05) between the γ(min)of APS and the corresponding INS-APS.In vivo experi-ments showed a significant glucose level decrease and insulin absorptionincrease (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 histopatho-logical observation indicated that INS-APS could alleviate lung injury.Conclusion:The most potent hypoglycemic effect and insulin absorption increase in this studywere obtained with INS/DPPC/Tyl.According to the results,there was a linearcorrelation between the γ_(min)and relative bioavailability of INS-APS,suggesting apossible effect of the γ_(min) of carriers on the in vivo absorption of insulin.APS,DPPC/Tyl,and DPPC/PG dispersions might be the most efficient insulin pulmo-nary delivery carriers in achieving a lower γ_(min),enhancing insulin absorption,anddecreasing lung injury. Aim: The relative bioavailabilities and effects on lung injury alleviation of 4 insu-lin-artificial pulmonary surfactant (INS-APS) preparations were studied in normalrats. The relationship between the minimal surface tension (γ_ (min)) 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 DPPC / L-α-phosphatidyl-DL-glycone erlenium salt (PG), DPPC / Tyl] were prepared by thin-film sonication method and direct sonication.The γ_ (min) of 4 APS dispersions was examined with andwithout INS by pulsating with a bubble surface tensiometer. In vivo experimentswere performed in which serum glucose change and the insulin level were mea-sured by an enzymatic glucose reagent kit and a radioimmunology assay kit afterIT to rats. reduction in lung injury by INS-APS following 7 d of consecutiveadministration was evaluated by the pulmonary edema index (the weight ratio of wet lung to dry lung) and histopathology examination. Results: The γ_ (min) of all APs dispersions were below 10 mN / m.There was no significant difference (P> 0.05) between the γ (min) of APS and the corresponding INS-APS.In vivo experi-ments showed a significant glucose level decrease and insulin absorption increase (P <0.05) in the presence of APS, compared to the insulin solution alone. Virus the results, we found that the pulmonary edema index values of all the INS-APS groups were significantly 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 histopatho-logical observations indicated that INS-APS could alleviate lung injury. Conlusion: The most potent hypoglycemic effect and insulin absorption increase in this study we acquired with INS / DPPC / Tyl. According to the results, there was a linear relationship between the γ_ (min) and relative bio availcapable of INS-APS, suggesting apossible effect of the γ_ (min) of carriers on the in vivo absorption of insulin. APS, DPPC / Tyl, and DPPC / PG dispersions might be the most efficient insulin pulmo-delivery vectors in achieving a lower γ_ (min), enhancing insulin absorption, and decreasing lung injury.
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