A microfluidic system is presented to generate multiple daughter droplets from a mother droplet, by the multistep hydrodynamic division of the mother droplet at multiple branch points in a microchannel. A microchannel network designed based on the resistive circuit model enables us to control the distribution ratio of the flow rate, which dominates the division ratios of the mother droplets. We successfully generated up to 15 daughter droplets from a mother droplet with a variation in diameter of less than 2%. In addition, we examined factors affecting the division ratio, including the average fluid velocity, interfacial tension, fluid viscosity, and the distribution ratio of volumetric flow rates at a branch point. Additionally, we actively controlled the volume of the mother droplets and examined its influence on the size of the daughter droplets, demonstrating that the size of the daughter droplets was not significantly influenced by the volume of the mother droplet when the distribution ratio was properly controlled. The presented system for controlling droplet division would be available as an innovative means for preparing monodisperse emulsions from polydisperse emulsions, as well as a technique for making a microfluidic dispenser for digital microfluidics to analyze the droplet compositions.
The present study aimed to develop inhalable poly (lactic-co-glycolic acid) (PLGA)-based microparticles of salmon calcitonin (sCT) for sustained pharmacological action by the fine droplet drying (FDD) process, a novel powderization technique employing printing technologies. PLGA was selected as a biodegradable carrier polymer for sustained-release particles of sCT (sCT/SR), and physicochemical characterizations of sCT/SR were conducted. To estimate the in vivo efficacy of the sCT/SR respirable powder (sCT/SR-RP), plasma calcium levels were measured after intratracheal administration in rats. The particle size of sCT/SR was 3.6 µm, and the SPAN factor, one of the parameters to present the uniformity of particle size distribution, was calculated to be 0.65. In the evaluation of the conformational structure of sCT, no significant changes were observed in sCT/SR even after the FDD process. The drug release from sCT/SR showed a biphasic pattern with an initial burst and slow diffusion in simulated lung fluid. sCT/SR-RP showed fine inhalation performance, as evidenced by a fine particle fraction value of 28% in the cascade impactor analysis. After the insufflation of sCT samples (40 µg-sCT/kg) in rats, sCT/SR-RP could enhance and prolong the hypocalcemic action of sCT possibly due to the sustained release and pulmonary absorption of sCT. From these observations, the strategic application of the FDD process could be efficacious to provide PLGA-based inhalable formulations of sCT, as well as other therapeutic peptides, to enhance their biopharmaceutical potentials.
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