Micro/Nanophysics Research Laboratory, RMIT University , Melbourne, Victoria 3001, Australia.
Murdoch Children's Research Institute , Parkville, Victoria 3052, Australia.
Biomicrofluidics. 2015 Apr 8;9(5):052603. doi: 10.1063/1.4917181. eCollection 2015 Sep.
Nebulizers have considerable advantages over conventional inhalers for pulmonary drug administration, particularly because they do not require coordinated breath actuation to generate and deliver the aerosols. Nevertheless, besides being less amenable to miniaturization and hence portability, some nebulizers are prone to denature macromolecular drugs due to the large forces generated during aerosolization. Here, we demonstrate a novel portable acoustomicrofluidic device capable of nebulizing epidermal growth factor receptor (EGFR) monoclonal antibodies into a fine aerosol mist with a mass median aerodynamic diameter of approximately 1.1 μm, optimal for deep lung deposition via inhalation. The nebulized monoclonal antibodies were tested for their stability, immunoactivity, and pharmacological properties, which confirmed that nebulization did not cause significant degradation of the antibody. In particular, flow cytometry demonstrated that the antigen binding capability of the antibody is retained and able to reduce phosphorylation in cells overexpressing the EGFR, indicating that the aerosols generated by the device were loaded with stable and active monoclonal antibodies. The delivery of antibodies via inhalation, particularly for the treatment of lung cancer, is thus expected to enhance the efficacy of this protein therapeutic by increasing the local concentration where they are needed.
雾化器在肺部药物给药方面相对于传统的吸入器具有相当大的优势，特别是因为它们不需要协调的呼吸动作来产生和输送气溶胶。然而，除了不太适合小型化和便携性之外，一些雾化器由于在雾化过程中产生的大力量而容易使大分子药物变性。在这里，我们展示了一种新颖的便携式声微流控装置，能够将表皮生长因子受体（EGFR）单克隆抗体雾化成细的气溶胶雾，其质量中值空气动力学直径约为 1.1μm，通过吸入可实现深肺部沉积的最佳效果。对雾化后的单克隆抗体进行稳定性、免疫活性和药理学特性测试，结果证实雾化不会导致抗体的显著降解。特别是，流式细胞术表明，抗体的抗原结合能力得以保留，并且能够减少过度表达 EGFR 的细胞中的磷酸化，表明该装置产生的气溶胶中载有稳定且有效的单克隆抗体。通过吸入输送抗体，特别是用于治疗肺癌，有望通过增加所需的局部浓度来提高这种蛋白治疗的疗效。
