Center for Molecular Nutrition and Sensory Disorders, The Taste and Smell Clinic, Washington, DC, USA.
Nutrition. 2010 Jan;26(1):33-9. doi: 10.1016/j.nut.2009.08.001.
After discovery of insulin as a hypoglycemic agent in 1921 various routes of administration to control blood glucose were attempted. These included subcutaneous, oral, rectal, sublingual, buccal, transdermal, vaginal, intramuscular, intrapulmonary and intranasal delivery systems. While each delivery system controlled hyperglycemia the subcutaneous route was given priority until 2006 when the Federal Drug Administration (FDA) approved the first commercially available pulmonary inhaled insulin.
A review of major publications dealing with intrapulmonary administration of insulin was made to understand the physiological basis for its use, its efficacy in controlling hyperglycemia, its side effects and a comparison of its efficacy with other delivery methods.
The large surface area of the lung, its good vascularization, capacity for solute exchange and ultra thin membranes of alveolar epithelia are unique features that facilitate pulmonary insulin delivery. Large lung surface area ( approximately 75 m(2)) and thin alveolar epithelium ( approximately 0.1-0.5 microm) permit rapid drug absorption. First pass metabolism avoids gastrointestinal tract metabolism. Lung drug delivery depends upon a complex of factors including size, shape, density, charge and pH of delivery entity, velocity of entry, quality of aerosol deposition, character of alveoli, binding characteristics of aerosol on the alveolar surface, quality of alveolar capillary bed and its subsequent vascular tree. Many studies were performed to optimize each of these factors using several delivery systems to enhance pulmonary absorption. Availability was about 80% of subcutaneous administration with peak activity within 40-60 min of administration. Intranasal insulin delivery faces a smaller surface area ( approximately 180 cm(2)) with quite different absorption characteristics in nasal epithelium and its associated vasculature. Absorption depends upon many factors including composition and character of nasal mucus. Absorption of intranasal insulin resulted in a faster absorption time course than with subcutaneous insulin.
After many studies the FDA approved Pfizer's product, Exubera, for intrapulmonary insulin delivery. While the system was effective its expense and putative side effects caused the drug company to withdraw the drug from the marketplace. Attempts by other pharmaceutical companies to use intrapulmonary insulin delivery are presently being made as well as some minor attempts to use intranasal delivery systems.
1921 年发现胰岛素作为降血糖药物后，人们尝试了各种给药途径来控制血糖。这些途径包括皮下、口服、直肠、舌下、颊部、透皮、阴道、肌肉内、肺内和鼻内给药系统。虽然每种给药系统都能控制高血糖，但直到 2006 年，美国食品和药物管理局（FDA）批准第一种商业上可获得的肺内吸入胰岛素，皮下给药途径才被优先考虑。
对涉及肺内给予胰岛素的主要出版物进行了回顾，以了解其使用的生理基础、控制高血糖的疗效、副作用，并将其疗效与其他给药方法进行比较。
肺具有较大的表面积、良好的血管化、溶质交换能力和极薄的肺泡上皮细胞，这些独特的特征促进了肺内胰岛素的传递。较大的肺表面积（约 75 m2）和极薄的肺泡上皮（约 0.1-0.5 µm）允许快速药物吸收。首过代谢避免了胃肠道代谢。肺内药物输送取决于多个因素，包括输送实体的大小、形状、密度、电荷和 pH 值、进入速度、气溶胶沉积质量、肺泡特性、气溶胶在肺泡表面的结合特性、肺泡毛细血管床的质量及其随后的血管树。许多研究使用几种输送系统来优化这些因素中的每一个，以增强肺吸收。肺内给药的生物利用度约为皮下给药的 80%，给药后 40-60 分钟达到峰值活性。鼻内胰岛素给药的表面积较小（约 180 cm2），鼻腔上皮及其相关血管的吸收特性也大不相同。吸收取决于多种因素，包括鼻黏液的组成和特性。与皮下胰岛素相比，鼻内胰岛素的吸收时间更快。
经过多次研究，美国食品和药物管理局批准辉瑞公司的产品 Exubera 用于肺内胰岛素输送。虽然该系统有效，但由于其费用和潜在的副作用，制药公司已将该药物从市场上撤回。其他制药公司目前正在尝试使用肺内胰岛素输送，以及一些使用鼻内输送系统的小尝试。
