Center for Medical Research, Medical University of Graz, Graz, Austria; Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, University of Graz, Austria.
Eur J Pharm Biopharm. 2021 Jun;163:198-211. doi: 10.1016/j.ejpb.2021.04.003. Epub 2021 Apr 11.
Oral inhalation is the preferred route for delivery of small molecules to the lungs, because high tissue levels can be achieved shortly after application. Biologics are mainly administered by intravenous injection but inhalation might be beneficial for the treatment of lung diseases (e.g. asthma). This review discusses biological and pharmaceutical challenges for delivery of biologics and describes promising candidates. Insufficient stability of the proteins during aerosolization and the biological environment of the lung are the main obstacles for pulmonary delivery of biologics. Novel nebulizers will improve delivery by inducing less shear stress and administration as dry powder appears suitable for delivery of biologics. Other promising strategies include pegylation and development of antibody fragments, while carrier-encapsulated systems currently play no major role in pulmonary delivery of biologics for lung disease. While development of various biologics has been halted or has shown little effects, AIR DNase, alpha1-proteinase inhibitor, recombinant neuraminidase, and heparin are currently being evaluated in phase III trials. Several biologics are being tested for the treatment of coronavirus disease (COVID)-19, and it is expected that these trials will lead to improvements in pulmonary delivery of biologics.
口服是将小分子递送至肺部的首选途径，因为在施用后不久即可达到高组织水平。生物制剂主要通过静脉注射给药，但吸入可能有益于治疗肺部疾病（例如哮喘）。本文综述了生物制剂递送至肺部的生物学和药物学挑战，并描述了有前途的候选药物。在气溶胶化过程中蛋白质的稳定性不足和肺部的生物学环境是生物制剂肺部递送至的主要障碍。新型雾化器通过诱导较小的剪切力来改善输送，干粉给药似乎适合生物制剂的递送。其他有前途的策略包括聚乙二醇化和抗体片段的开发，而载体包封系统目前在肺部递送至肺部疾病的生物制剂中没有发挥主要作用。虽然各种生物制剂的开发已经停止或效果甚微，但 AIR DNase、α1-蛋白酶抑制剂、重组神经氨酸酶和肝素目前正在进行 III 期临床试验评估。一些生物制剂正在测试用于治疗冠状病毒病（COVID-19），预计这些试验将导致生物制剂肺部递送至的改善。
