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Modeling of Water Uptake into Polymeric Aerosol Particulates Deposited on the Lung Surface Neil Gupta Biological Transport December 12 2001 Abstract Inhalation of aerosolized drugs holds promise as a means to treat localized disease states within the lung and may also represent an ideal method for drug delivery to the systemic circulation The use of polymer-based aerosol carriers for controlled drug delivery via the lung is an approach that may improve the duration and effectiveness of drugs delivered to the respiratory tract However the ability to optimize new formulations for pulmonary drug delivery has been limited by the inability to closely mimic the conditions the particles encounter in the various regions of the lung Conventional complete immersion methods used to characterize microparticle water uptake rates polymer degradation kinetics and drug diffusion rates may not be relevant for particles designed for inhalation due to the extremely thin aqueous layers in the lungs In this paper I discuss the forces on a particle at the air-surfactant-particle interface used to determine the extent of submersion Then I model the water uptake into particles completely immersed in liquid and compare it to water uptake into spherical particles partially submersed in liquid From published water contact angles it was found that 10 mm PLGA 5050 particles would be submersed 68 mm into the liquid phase more hydrophobic PLGA 9010 particles would be submersed 61 mm The aqueous layers in the lung have a significantly lower surface tension than water Particles will therefore be submerged more into the lung liquid than in water and may be completely submerged Concentration profiles for 5 mm particles completely submerged in an aqueous solution showed the concentration within the particles increases with time until a steady value is reached in approximately 67 hours Water uptake into particles submersed in humidified air depends on adsorption and condensation of water on the particle
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