胰岛素脂质混悬液肺部给药的生物利用度及对肺部损伤的初步考察

目的 研究胰岛素脂质混悬液(ILS)经正常大鼠气管滴注给药后肺部吸收的生物利用度,并对给药造成的肺损伤进行初步考察。方法 以薄膜-超声分散法制备ILS,结合药效学和药动学考察气管滴注给药后的药理相对生物利用度和药物相对生物利用度;以肺水肿指数和肺组织病理改变为指标考察肺部给药后对肺部造成的损伤。结果ILS以1、4、8u/kg肺部给药后其药理相对生物利用度分别为65.2％、50.8％和37.1％,药物相对生物利用度分别为67.9％.40.9％和31.7％,均随给药剂量增加而降低;连续7d气管滴注给药后,ILS给药组的肺水肿指数和肺组织病理改变与普通胰岛素溶液给药后相比具有显著性差异,前者优于后者并接近正常组。结论ILS肺部给药后可达到较高的生物利用度,同时可减轻肺部给药后的肺损伤

Study on the bioavailability and initial investigation on the rat following pulmonary delivery of insulin lipid suspension

Purpose To study the bioavailability of pulmonary administered insulin lipid suspension (ILS) in normal rats and to investigate the damage to the lung after administration. Methods ILS was prepared by thin-film sonication method. Following intratracheally instillation of ILS, the relative pharmacological bioavailability (f % ) and relative bioavailability ( F % ) of ILS were calculated based on the area above the curve (AAC) and the area under the curve (AUC) compared with subcutaneous injection of insulin PBS, respectively. The changes of pulmonary edema index and pathology of lungs were investigated to evaluate the severity of the damage to lungs. Results As ILS was administered at different doses (1,4,8u/kg), the f % values reached 65.2 %,50.8 % and 37.1 %, respectively, and the F % values reached 67.9 %,40.9 % arid 31.7 % , separately. The results showed that the following intratracheally instillation for 7 consecutive days, the pulmonary edema index and pathological changes of lung tissue in ILS group were significantly different from those in regular insulin solution group and close to those in normal one. Conclusion The results showed that ILS could achieve higher bioavailability and reduce the severity of damage to rat lung following pulmonary delivery.