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Biology subjects

Fromen, C. A.

Publications and source records attributed to Fromen, C. A..

2 recordsLinked to original sources

Computational Modeling of Aerosol Particle Transport through Lung Mucosa

Delivery of aerosols to the lung has great potential for the treatment of various lung diseases. However, the lungs are coated by a protective mucus layer whose complex properties make this form of delivery difficult. Mucus is a non-Newtonian fluid and is cleared from the lungs over time by ciliated cells. Further, its gel-like structure hinders the diffusion of particles through it. Any aerosolized treatment of lung diseases must have certain properties to circumvent the mucosal barrier, and these properties may vary between diseases, drugs, and patients. Using computational fluid dynamics, a model of this mucus layer was constructed to simulate the convective and diffusive transport of impacted aerosol particles. The model predicts the dosage fraction of particles of a certain size that penetrate the mucus and reach the underlying tissue, as well as the distance downstream of the dosage site where epithelial concentration is maximized. Reactions that may occur in solution are also considered, with simulated data for the interaction of a model virus and antibody. The model is modular so that various lung regions and patient health states may be simulated.

bioengineering↗

Nanoparticle Internalization Promotes the Survival of Primary Macrophages

Macrophages, a class of tissue resident innate immune cells, are responsible for sequestering foreign objects through the process of phagocytosis, making them a promising target for immune-modulation via particulate engineering. Here, we report that nanoparticle (NP) dosing and cellular internalization via phagocytosis significantly enhances survival of ex vivo cultures of primary bone marrow-derived, alveolar, and peritoneal macrophages over particle-free controls. The enhanced survival is attributed to suppression of caspase-dependent apoptosis and is linked to phagocytosis and lysosomal signaling, which was also found to occur in vivo. Uniquely, poly(ethylene glycol)-based NP treatment does not alter macrophage polarization or lead to inflammatory effects. The enhanced survival phenomenon is also applicable to NPs of alternative chemistries, indicating the potential universality of this phenomenon with relevant drug delivery particles. These findings provide a framework for extending the lifespan of primary macrophages ex vivo for drug screening, vaccine studies, and cell therapies and has implications for any in vivo particulate immune-engineering applications.

bioengineering↗