1. Development and validation of low-shear nebulization method: The primary technical focus of this fellowship involved the prototyping and systematic evaluation of a soft aerosolization system specifically engineered for fragile biopharmaceuticals. A central component of this work was a comparative analysis of structural preservation across different nebulization methods, using a commercial pulmonary surfactant as a model. This surfactant—a complex mixture of lipids and proteins secreted by type II alveolar cells—is critical for regulating surface tension at the air–liquid interface of the alveoli and is essential for respiratory function.
While conventional vibrating mesh nebulization was found to disrupt these delicate molecular arrangements, our results demonstrated that the low-shear spray technique maintained the structural integrity of the complex surfactant. Consequently, the biophysical functionality was significantly better preserved, which represents a substantial increase in potential therapeutic effectiveness compared to existing clinical technologies.
2. A simple prediction for drop coalescence: To optimize drug delivery, we investigated the mechanisms of drop coalescence during mist generation. In pulmonary therapy, the deposition site within the airway is dictated by the aerodynamic diameter: droplets between 5–10 μm typically deposit in the central airways, whereas those between 1–5 μm reach the lower respiratory regions. Achieving a narrow droplet size distribution is therefore critical for targeted delivery. However, in many cases, drops tend to coalesce once they approach each other.
We explored how fluid properties, namely viscosity and surface tension, determine drop coalescence regimes. We proposed a novel scaling approach using a dimensionless crossover function that characterizes the smooth transition between viscous and inertial limits. This theoretical framework successfully predicts the regimes and crossover of drop coalescence, providing a robust principle for controlling aerosol characteristics during device operation.
3. Investigations into mucus rheology: The final stage of the project examined the interaction between drug particles and the airway surface, which is covered by a protective, water-based polymeric mucus. This mucus is a viscoelastic fluid with a mesh-like structure that exhibits gel-like properties at the macroscopic level but behaves as a low-viscosity fluid at the microscopic scale.
Using artificial mucus models designed to mimic the rheological profiles of diseased states (such as COPD and asthma), we analyzed the diffusivity of particles within mucus. Our findings revealed that the structural mesh size is a significantly more dominant factor in particle mobility than the macroscopic rheology of the mucus. This discovery provides critical insights for the future design of drug carriers intended to penetrate the mucus barrier in patients.
