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Aerosolization of poly(sulfobetaine) microparticles that encapsulate therapeutic antibodies.

Biomater Adv 2024 March 26
Pulmonary delivery of protein therapeutics poses significant challenges that have not been well addressed in the research literature or practice. In fact, there is currently only one commercial protein therapeutic that is delivered through aerosolization and inhalation. In this study, we propose a drug delivery strategy that enables a high-concentration dosage for the pulmonary delivery of antibodies as an aerosolizable solid powder with desired stability. We utilized zwitterionic polymers for their promising properties as drug delivery vehicles and synthesized swellable, biodegradable poly(sulfo-betaine) (pSB) microparticles. The microparticles were loaded with Immunoglobulin G (IgG) as a model antibody. We quantified the microparticle size and morphology, and the particles were found to have an average diameter of 1.6 μm, falling within the optimal range (~1-5 μm) for pulmonary drug delivery. In addition, we quantified the impact of the crosslinker to monomer ratio on particle morphology and drug loading capacity. The results showed that there is a trade-off between desired morphology and drug loading capacity as the crosslinker density increases. In addition, the particles were aerosolized, and our data indicated that the particles remained intact and retained their initial morphology and size after aerosolization. The combination of morphology, particle size, antibody loading capacity, low cytotoxicity, and ease of aerosolization support the potential use of these particles for pulmonary delivery of protein therapeutics.

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