Enhanced macrophage uptake of spray-dried phosphatidylserine-loaded microparticles for pulmonary drug delivery applications

Macrophages are an integral part of the innate immune system and act as a first line of defense to pathogens; however, macrophages can be reservoirs for pathogens to hide and replicate. Tuberculosis, influenza virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are common diseases whose pathogens are uptaken into macrophages. Current treatments for diseases such as these are limited by the therapeutic delivery method, which typically involves systemic delivery in large, frequent doses. This study aims to overcome this limitation via the development of an inhalable dry powder microparticle (MP) formulation capable of targeted drug delivery to alveolar macrophages in addition to controlled release of a therapeutic. A simple one-step spray drying method was used to synthesize acetalated dextran (Ac-Dex) MP loaded with the model therapeutic, curcumin, and 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS), which is a phospholipid that induces ligand-receptor mediated macrophage phagocytosis. The resulting MP exhibited significantly more uptake by RAW 264.7 macrophages in comparison to MP without DPPS, and it was shown that DPPS-mediated uptake was macrophage specific. The particles exhibited pH-responsive release and in vitro aerosol dispersion analysis confirmed the MP can be effectively aerosolized for pulmonary delivery. Overall, the described MP has the potential to improve treatment efficacy for macrophage-associated diseases.