Targeted delivery of antibodies through the lungs can increase the utilization efficiency of therapeutics compared to intravenous injection. Antibodies are sensitive and unstable, however, and their potential immunogenicity limits the possibility of delivering them to the lungs via inhalation. Current methods for pulmonary delivery of antibodies have significant drawbacks. For example, nebulizing a solution of antibody denatures the protein during the process due to high shear force and high pressure. Delivery of antibodies as dry powder requires an architecture small enough (~ 1-5 μm) for antibody particles, and proteins could be denatured in the particle manufacturing process. The denatured antibodies not only reduce the overall efficacy but can also aggregate and induce severe immunogenicity. Antibodies must be protected and stabilized to maintain their efficacy and not be cleared by the immune system in the lungs.
Zwitterionic polymers are dual-charged hydrophilic materials known for their biocompatibility. These materials are typically synthesized by zwitterionic monomers to protect proteins, thereby enhancing biological function. They can protect antibodies from environmental influences, such as during pulmonary delivery, while also facilitate the delivery of these antibodies for therapeutic applications. In our previous work, we designed aerosolizable zwitterionic poly(sulfo betaine) (pSB) microparticles and controlled their diameter within the range of 1-5 μm to avoid mucociliary clearance. We encapsulated IgG as a model antibody and confirmed that pSB microparticles can safeguard IgG from harsh conditions. However, we found that the IgG encapsulation efficiency of pSB microparticles was only about 10%. To improve the loading efficiency of pSB microparticles, we utilized polyethylene glycol (PEG) as a porogen to create porous pSB microparticles. We examined the effect of porogen ratio on morphology, density, water content, degradability, and antibody encapsulation capacity. Fourier transform infrared spectroscopy was carried out to ensure the removal of PEG. A human lung fibroblast cell viability test was carried out to measure the in vitro cytotoxicity of porous pSB microparticles. Additionally, we released IgG from pSB microparticles, and using an ELISA assay, we quantified the activity of the released IgG. The primary outcome of our research is the development of a potential inhalable antibody carrier for pulmonary delivery with low cytotoxicity.
