Microsphere-based controlled release technologies have been utilized for the long-term delivery of proteins,\npeptides and antibiotics, although their synthesis poses substantial challenges owing to formulation\ncomplexities, lack of scalability, and cost. To address these shortcomings, we used the electrospray process\nas a reproducible, synthesis technique to manufacture highly porous (>94%) microspheres while maintaining\ncontrol over particle structure and size. Here we report a successful formulation recipe used to generate\nspherical poly(lactic-co-glycolic) acid (PLGA) microspheres using the electrospray (ES) coupled with a novel\nthermally induced phase separation (TIPS) process with a tailored Liquid Nitrogen (LN2) collection scheme.\nWeshow how size, shape and porosity of resulting microspheres can be controlled by judiciously varying\nelectrospray processing parameters and we demonstrate examples in which the particle size (and porosity)\naffect release kinetics. The effect of electrospray treatment on the particles and their physicochemical properties\nare characterized by scanning electron microscopy, confocal Raman microscopy, thermogravimetric\nanalysis and mercury intrusion porosimetry. The microspheres manufactured here have successfully\ndemonstrated long-term delivery (i.e. 1 week) of an active agent, enabling sustained release of a dye with\nminimal physical degradation and have verified the potential of scalable electrospray technologies for an\ninnovative TIPS-based microsphere production protocol.
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