Sustained release of a model water-soluble compound via dry powder aerosolizable acetalated dextran microparticles

Objective: To design and characterize aerosol microparticles (MP) to provide sustained release of the water-soluble compound sulforhodamine B (SRB) and achieve effective aerosol dispersion.

Significance: Modulating the release of water-soluble compounds remains a challenge in pulmonary drug delivery.

Methods: SRB and water made up an aqueous solution, while acetalated dextran (Ac-Dex) and isopropyl alcohol made up an organic solution. The two solutions were mixed together, and the solution was spray dried to produce MP. MP were characterized for morphology, size, release kinetics, aerosol dispersion, and cellular interactions.

Results: Ac-Dex MP exhibited corrugated morphology and aerodynamic diameters from 2.06 to 2.86 μm. MP deposited in all stages of a Next Generation Impactor, with >90% fine particle fraction. MP exhibited encapsulation efficiencies >129% with SRB loading values up to 16.7 μg SRB/mg MP. MP exhibited sustained release of SRB at pH 7 and fast release at pH 5. In vitro experiments showed minimal cytotoxicity, successful uptake of MP in epithelial cells, and no disruption to the integrity of epithelial monolayers.

Conclusions: Ac-Dex MP systems demonstrated the ability to provide sustained the release of a water-soluble therapeutic in addition to effective aerosol dispersion for pulmonary applications.