Brain Joseph D
Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Diabetes Technol Ther. 2007 Jun;9 Suppl 1:S4-S15. doi: 10.1089/dia.2007.0228.
In contrast to other interfaces between the outer and inner environment, such as the skin and gastrointestinal tract, the lungs are ideally suited for the delivery of polypeptides and proteins to the systemic circulation. There is a wealth of experience from aerosol physics and lung biology to support the idea that insulin delivery via the lungs is an effective strategy. The elaborate branching network of airways, the extensive surface area of the deep lung, and the thin air-blood barrier make it possible to deliver insulin and other proteins to the parenchyma, where it can be absorbed into the pulmonary circulation and become available throughout the body. Protein-containing aerosols in inspired air deposit throughout the respiratory tract because of the following forces: gravity, diffusion, and inertial impaction. Lung anatomy, breathing pattern, and particle size determine the influence of these forces. Once deposited in the lungs, most protein-containing formulations quickly dissolve in airway or alveolar lining fluid. Then, a significant fraction of insulin is transported across the air-blood barrier into the blood, where it continues to be biologically active. A substantial fraction--usually the majority--is cleared from the lungs or degraded within the lungs.
与皮肤和胃肠道等内外环境之间的其他界面不同，肺非常适合将多肽和蛋白质输送到体循环。气溶胶物理学和肺生物学有丰富的经验支持通过肺部输送胰岛素是一种有效策略的观点。气道的精细分支网络、深部肺组织的广泛表面积以及薄薄的气血屏障，使得将胰岛素和其他蛋白质输送到实质组织成为可能，在那里它们可以被吸收进入肺循环并在全身发挥作用。吸入空气中含蛋白质的气溶胶由于重力、扩散和惯性撞击等力而沉积在整个呼吸道。肺部解剖结构、呼吸模式和颗粒大小决定了这些力的影响。一旦沉积在肺部，大多数含蛋白质的制剂会迅速溶解在气道或肺泡内衬液中。然后，相当一部分胰岛素会穿过气血屏障进入血液，在那里它仍然具有生物活性。相当一部分——通常是大部分——会从肺部清除或在肺部降解。
