Medspray BV, Colosseum 23, 7521 PV Enschede, The Netherlands.
School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
Curr Opin Pharmacol. 2017 Oct;36:52-57. doi: 10.1016/j.coph.2017.07.015. Epub 2017 Aug 30.
Oral inhalation offers the opportunity of targeting drugs locally to different regions of the respiratory tract or alternatively, using the high surface area of the alveoli for systemic delivery. Pulmozyme and the inhaled insulins (i.e. Exubera and Afrezza) are examples of the scope of pulmonary drug delivery of biopharmaceuticals-albeit with strikingly different commercial success. Particularly, the failure of Exubera and the subsequent overreactions (e.g. the unsubstantiated lung cancer fear), lastingly stunned the field of systemically inhaled protein and peptide drugs. Building on the lessons learned from these early products, a new wave of inhaled biomolecules has recently entered clinical trials. Moreover, oral inhalation has become an attractive alternative for the delivery of small molecules with difficult oral pharmacokinetics and/or extensive liver first-pass metabolism. Advances in inhaler design and our increased understanding of lung physiology continue to make oral inhalation of complex drugs an attractive therapeutic option.
口服吸入为靶向药物提供了机会，可以将药物局部递送到呼吸道的不同区域，或者利用肺泡的高表面积进行全身递送。Pulmozyme 和吸入型胰岛素（即 Exubera 和 Afrezza）是生物制药肺部药物输送范围的例子，尽管它们的商业成功程度截然不同。特别是 Exubera 的失败以及随后的过度反应（例如毫无根据的肺癌恐惧），给系统吸入蛋白质和肽类药物的领域带来了持久的冲击。从这些早期产品中吸取教训，最近一波新的吸入生物分子已进入临床试验。此外，口服吸入已成为具有困难口服药代动力学和/或广泛肝脏首过代谢的小分子药物的一种有吸引力的替代方法。吸入器设计的进步和我们对肺生理学的认识不断提高，使复杂药物的口服吸入成为一种有吸引力的治疗选择。
