INSERM, Centre D'Etude Des Pathologies Respiratoires, Universite François Rabelais de Tours, 10 Boulevard Tonnellé, U1100F-37032, Tours, France.
University of Tours, Tours, France.
Drug Deliv Transl Res. 2021 Aug;11(4):1625-1633. doi: 10.1007/s13346-021-00967-w. Epub 2021 Mar 25.
Respiratory infections are life-threatening and therapeutic antibodies (Ab) have a tremendous opportunity to benefit to patients with pneumonia due to multidrug resistance bacteria or emergent virus, before a vaccine is manufactured. In respiratory infections, inhalation of anti-infectious Ab may be more relevant than intravenous (IV) injection-the standard route-to target the site of infection and improve Ab therapeutic index. One major challenge associated to Ab inhalation is to prevent protein instability during the aerosolization process. Ab drug development for IV injection aims to design a high-quality product, stable to different environment stress. In this study, we evaluated the suitability of Ab formulations developed for IV injection to be extended for inhalation delivery. We studied the aerosol characteristics and the aggregation profile of three Ab formulations developed for IV injection after nebulization, with two mesh nebulizers. Although the formulations for IV injection were compatible with mesh nebulization and deposition into the respiratory tract, the Ab were more unstable during nebulization than exposition to a vigorous shaking. Overall, our findings indicate that Ab formulations developed for IV delivery may not easily be repurposed for inhalation delivery and point to the requirement of a specific formulation development for inhaled Ab.
呼吸道感染具有生命威胁性，而治疗性抗体 (Ab) 有巨大的机会使患有多重耐药菌或新兴病毒肺炎的患者受益，而无需制造疫苗。在呼吸道感染中，吸入抗感染 Ab 可能比静脉注射 (IV) 注射——标准途径——更能针对感染部位，并提高 Ab 的治疗指数。与 Ab 吸入相关的一个主要挑战是在雾化过程中防止蛋白质不稳定。用于 IV 注射的 Ab 药物开发旨在设计一种高质量的产品，对不同的环境压力稳定。在这项研究中，我们评估了为 IV 注射开发的 Ab 制剂扩展用于吸入给药的适用性。我们研究了三种为 IV 注射开发的 Ab 制剂在雾化后的雾化特性和聚集特性，使用了两种网孔雾化器。尽管 IV 注射用的制剂与网孔雾化器兼容，并且可以沉积到呼吸道中，但 Ab 在雾化过程中比剧烈晃动时更不稳定。总体而言，我们的研究结果表明，为 IV 输送开发的 Ab 制剂可能不容易重新用于吸入输送，并指出需要专门为吸入 Ab 开发制剂。
