Wenzhou Medical College, Wenzhou, Zhejiang Province, China.
Diabetes Technol Ther. 2011 Oct;13(10):1013-21. doi: 10.1089/dia.2011.0113. Epub 2011 Jul 11.
Gas-filled phospholipid-based ultrasonic microbubbles (PUMs) are widely used in diagnostic imaging. The micro- or nanoparticle size and the physiochemical nature of shell provide the potential for a new way to improve pulmonary absorption for peptides and proteins.
Male Sprague-Dawley rats were fasted for 12 h. Then insulin solution and insulin-PUM mixture solution were administered by intratracheal instillation. The hypoglycemic effect was observed to evaluate insulin absorption after lung administration. Fluorescein isothiocyanate-dextran (molecular mass, 4 kDa) was used as the index of evaluating drug alveolar deposition and absorption by visualization techniques.
Administration of insulin solution containing PUMs significantly reduced the blood glucose levels of Sprague-Dawley rats, compared with administration of insulin-only solution. The minimum reductions of the blood glucose concentration produced by insulin solution containing PUMs and by an insulin-only solution reached 60.81% and 34.60% of the initial glucose levels, respectively, and their bioavailabilities relative to subcutaneous injection were 48.58% and 29.09%, respectively. Histopathological study of the lung showed no changes in the morphology of the pulmonary alveoli after administration to these drugs. Only a slight inflammatory cell infiltration in the alveoli could be found in some rats.
These results suggested that PUMs might be used as an effective way to improve pulmonary absorption for peptides and proteins.
充气体磷脂基超声微泡（PUMs）广泛用于诊断成像。其微纳米颗粒大小和壳的物理化学性质为改善肽类和蛋白质的肺吸收提供了新的途径。
雄性 Sprague-Dawley 大鼠禁食 12 小时。然后通过气管内滴注给予胰岛素溶液和胰岛素-PUM 混合物溶液。观察降血糖作用以评估肺给药后胰岛素的吸收。荧光素异硫氰酸酯-葡聚糖（分子量 4 kDa）用于通过可视化技术评估药物肺泡沉积和吸收的指标。
与仅给予胰岛素溶液相比，给予含有 PUM 的胰岛素溶液可显著降低 Sprague-Dawley 大鼠的血糖水平。含有 PUM 的胰岛素溶液和仅胰岛素溶液的最低血糖浓度降低分别达到初始葡萄糖水平的 60.81%和 34.60%，其相对于皮下注射的生物利用度分别为 48.58%和 29.09%。这些药物给药后肺的组织病理学研究显示，肺肺泡的形态没有变化。仅在一些大鼠中可以发现肺泡中轻微的炎症细胞浸润。
这些结果表明，PUMs 可能可作为改善肽类和蛋白质肺吸收的有效途径。
