Food and Drug Department, University of Parma, Parco Area Delle Scienze 27/a, Parma, Italy.
Interdepartmental Center Biopharmanet-Tec, University of Parma, Parco Area Delle Scienze Building 33, Parma, Italy.
Drug Deliv Transl Res. 2023 Oct;13(10):2653-2663. doi: 10.1007/s13346-023-01346-3. Epub 2023 Apr 25.
The nebulization of alpha-1 antitrypsin (AAT) for its administration to the lung could be an interesting alternative to parenteral infusion for patients suffering from AAT genetic deficiency (AATD). In the case of protein therapeutics, the effect of the nebulization mode and rate on protein conformation and activity must be carefully considered. In this paper two types of nebulizers, i.e., a jet and a mesh vibrating system, were used to nebulize a commercial preparation of AAT for infusion and compared. The aerosolization performance, in terms of mass distribution, respirable fraction, and drug delivery efficiency, as well as the activity and aggregation state of AAT upon in vitro nebulization were investigated. The two nebulizers demonstrated equivalent aerosolization performances, but the mesh nebulizer provided a higher efficiency in the delivery of the dose. The activity of the protein was acceptably preserved by both nebulizers and no aggregation or changes in its conformation were identified. This suggests that nebulization of AAT represents a suitable administration strategy ready to be translated to the clinical practice for delivering the protein directly to the lungs in AATD patients, either as a support therapy to parenteral administration or for subjects with a precocious diagnosis, to prevent the onset of pulmonary symptoms.
将α-1 抗胰蛋白酶（AAT）雾化用于肺部给药，可能是治疗 AAT 遗传缺陷（AATD）患者的一种有前途的替代方法，优于肠外输注。对于蛋白质治疗药物，雾化模式和速率对蛋白质构象和活性的影响必须仔细考虑。在本文中，我们使用两种类型的雾化器，即射流和网孔振动系统，对一种用于输注的商业 AAT 制剂进行雾化并进行了比较。研究了雾化的体外雾化时的气溶胶化性能（以质量分布、可吸入部分和药物传递效率表示）以及 AAT 的活性和聚集状态。这两种雾化器表现出相当的雾化性能，但网孔雾化器在输送剂量方面的效率更高。两种雾化器都能很好地保持蛋白质的活性，没有发现聚集或构象变化。这表明，AAT 的雾化代表了一种合适的给药策略，可以直接将蛋白质递送到 AATD 患者的肺部，无论是作为肠外给药的支持治疗，还是用于早期诊断的患者，以预防肺部症状的发生。
