Harris A S
Ferring Research, Malmö, Sweden.
J Drug Target. 1993;1(2):101-16. doi: 10.3109/10611869308996066.
Peptides are rapidly being developed as potential new therapeutic agents and the nasal route is being evaluated as a means of achieving systemic absorption. Current research in man is being directed at a number of polypeptides, including calcitonin, growth hormone releasing hormones (GHRH), insulin, gonadotropin hormone releasing hormones (GnRH) and vasopressin analogues. The underlying protective functions of the nose provide anatomical, temporal and enzymatic barriers to absorption of peptides. The nasal route is relatively unsuccessful when used for high molecular weight polypeptides. Penetration enhancers improve bioavailability but are poorly tolerated. Reproducibility of effect is highly variable, major contributing factors including the site of deposition and type of delivery system as well as changes in the mucous secretion and mucociliary clearance, compounded by the presence of allergy, hay fever and the common cold in treated subjects. The future potential for this route lies in development of effective and well tolerated formulations in highly accurate delivery systems for the chronic administration of peptides, enabling the replacement of impractical and invasive intravenous injections in patients on lifelong substitution treatment for various deficiency states.
肽类正迅速发展成为潜在的新型治疗药物，鼻腔给药途径正在作为实现全身吸收的一种方式进行评估。目前针对人类的研究集中在多种多肽上，包括降钙素、生长激素释放激素（GHRH）、胰岛素、促性腺激素释放激素（GnRH）和血管加压素类似物。鼻腔固有的保护功能为肽类的吸收提供了解剖学、时间和酶学屏障。当用于高分子量多肽时，鼻腔给药途径相对不太成功。渗透促进剂可提高生物利用度，但耐受性较差。效果的重现性差异很大，主要影响因素包括沉积部位和给药系统类型，以及粘液分泌和粘液纤毛清除的变化，此外，治疗对象存在过敏、花粉热和普通感冒也会使情况更加复杂。该给药途径未来的潜力在于开发高效且耐受性良好的制剂，用于高精度给药系统以长期给予肽类药物，从而在各种缺乏状态的终身替代治疗中，取代不实用且有创的静脉注射。
