Pulmonary monoclonal antibody delivery via a portable microfluidic nebulization platform

Abstract

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.

Future Trends in Nebulized Therapies for Pulmonary Disease

“…Surface acoustic wave nebulizers (SAWN) produce relatively short wavelength but high frequency (10 to 100 MHz) sound waves which travel along the surface of a liquid to generate aerosols. While there are currently few in vivo human studies, the potential of SAWN has been assessed for aerosol generation of peptides and demonstrated retained monoclonal antibody and antimicrobial integrity as well as bioactivity activity and appropriate particle size for deep lung penetration [45,46]. While SAWN offer similar benefits compared to vibrating mesh nebulizers (VMN) in terms of reduced shear stress, they may also prove less susceptible to clogging, particularly when particle suspensions or larger macromolecules are used.…”

Airway Delivery of Anti-influenza Monoclonal Antibodies Results in Enhanced Antiviral Activities and Enables Broad-Coverage Combination Therapies

“…For successful administration of nebulized protein biologics to the airway, it is important to establish optimal formulation and nebulization conditions that stabilize the protein during the nebulization process so that the integrity of the protein deposited in the lung is maintained (39,57,58). We have developed suitable nebulization conditions for the triple bnAb therapeutic combination CF-404 and have used nebulized CF-404 to successfully treat H1N1 infections in the mouse influenza infection model ( Figure 10).…”

Surface acoustic wave devices for chemical sensing and microfluidics: a review and perspective

“…To that end, the group has explored various shear-sensitive medicinal targets, including epidermal growth factor receptor (EGFR) monoclonal antibodies, antimicrobial peptide antibodies, plasmid DNA, and even stem cells to treat lung cancer and lung disease. 137,138,139,140 …”