In the last decade, biological drugs have rapidly proliferated and have now become an important therapeutic modality. This is because of their high potency, high specificity and desirable safety profile. The majority of biological drugs are peptide- and protein-based therapeutics with poor oral bioavailability. They are normally administered by parenteral injection (with a very few exceptions). Pulmonary delivery is an attractive non-invasive alternative route of administration for local and systemic delivery of biologics with immense potential to treat various diseases, including diabetes, cystic fibrosis, respiratory viral infection and asthma, etc. The massive surface area and extensive vascularisation in the lungs enable rapid absorption and fast onset of action. Despite the benefits of pulmonary delivery, development of inhalable biological drug is a challenging task. There are various anatomical, physiological and immunological barriers that affect the therapeutic efficacy of inhaled formulations. This review assesses the characteristics of biological drugs and the barriers to pulmonary drug delivery. The main challenges in the formulation and inhalation devices are discussed, together with the possible strategies that can be applied to address these challenges. Current clinical developments in inhaled biological drugs for both local and systemic applications are also discussed to provide an insight for further research.

中文翻译：

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生物药物的肺部输送

在过去的十年中，生物药物迅速普及，现已成为一种重要的治疗方式。这是因为它们的高效力、高特异性和理想的安全性。大多数生物药物都是基于肽和蛋白质的治疗药物，口服生物利用度较差。它们通常通过肠胃外注射给药（极少数例外）。肺部递送是一种有吸引力的非侵入性替代给药途径，用于局部和全身递送生物制剂，具有治疗各种疾病的巨大潜力，包括糖尿病、囊性纤维化、呼吸道病毒感染和哮喘等。肺内巨大的表面积和广泛的血管化肺部能够快速吸收并快速起效。尽管肺部输送有很多好处，但可吸入生物药物的开发仍然是一项具有挑战性的任务。有多种解剖学、生理学和免疫学障碍会影响吸入制剂的治疗效果。本综述评估了生物药物的特性和肺部药物输送的障碍。讨论了制剂和吸入装置中的主要挑战，以及可用于应对这些挑战的可能策略。还讨论了局部和全身应用的吸入生物药物的当前临床发展，为进一步的研究提供见解。