Liu F Y, Shao Z, Kildsig D O, Mitra A K
Department of Industrial and Physical Pharmacy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
Pharm Res. 1993 Feb;10(2):228-32. doi: 10.1023/a:1018934810512.
The effects of oligomerization and liposomal entrapment on pulmonary insulin absorption were investigated in rats using an intratracheal instillation method. The results indicated that both dimeric and hexameric insulins can be rapidly absorbed into the systemic circulation, producing a significant hypoglycemic response. Intratracheal instillation of insulin in two different oligomerized states has not resulted in any significant difference in the duration of hypoglycemic effect. However, the initial hypoglycemic response (first 10 min) obtained from intratracheal administration of 25 IU/kg hexameric insulin appears to be slower than that from the 25 IU/kg dimeric insulin, thereby suggesting that hexameric insulin may have a lower permeability coefficient across alveolar epithelium than the dimeric insulin. Intratracheal administration of insulin liposomes (dipalmitoylphosphatidyl choline:cholesterol, 7:2) led to facilitated pulmonary uptake of insulin and enhanced the hypoglycemic effect. Nevertheless, similar insulin uptake and pharmacodynamic response were obtained from both the physical mixture of insulin and blank liposomes and liposomally entrapped insulin.
采用气管内滴注法在大鼠中研究了寡聚化和脂质体包封对肺部胰岛素吸收的影响。结果表明，二聚体胰岛素和六聚体胰岛素均可迅速吸收进入体循环，产生显著的降糖反应。气管内滴注两种不同寡聚化状态的胰岛素，其降糖作用持续时间无显著差异。然而，气管内给予25IU/kg六聚体胰岛素的初始降糖反应（最初10分钟）似乎比给予25IU/kg二聚体胰岛素的反应慢，这表明六聚体胰岛素跨肺泡上皮的渗透系数可能低于二聚体胰岛素。气管内给予胰岛素脂质体（二棕榈酰磷脂酰胆碱：胆固醇，7:2）可促进肺部对胰岛素的摄取并增强降糖作用。然而，胰岛素与空白脂质体的物理混合物和脂质体包封的胰岛素均获得了相似的胰岛素摄取和药效学反应。
