Electrospray synthesis of monodisperse polymer particles in a broad (60 nm–2 μm) diameter range: guiding principles and formulation recipes

• PLGA particles are produced by electrospraying dilute conductive solutions at small flow rates.
• Uniform size particles are generated in the (60 nm–2 μm) range.
• Parameters affecting size are solution conductivity, flow rate and polymer concentration.
• The prevention of Coulomb fission by polymer chain entanglement preserves size uniformity.

This study reports on a methodology to control the size of polymer particles generated by the electrospray (ES) drying route, with emphasis on the generation of biodegradable polymer nanoparticles that are well suited for biomedical applications. The ability to produce spherical poly(lactic-co-glycolic) acid (PLGA) particles with and without encapsulated active agent, with relative standard deviation not exceeding 15%, was demonstrated over a remarkably broad (60 nm–2 μm) diameter range. By judiciously choosing ES parameters and solution properties, we can control the monodispersity and the size of the obtained particles, tailoring it to a specific application. The main parameters affecting particle size include solution electrical conductivity, flow rate and initial polymer volume fraction. Quasi-monodispersity at both the micro- and the more challenging nano-scale was achieved by avoiding Coulomb fission in the spray droplets, via entanglement of the polymer chains within the droplets rather than by charge neutralization. Guiding principles in the formulation of the solutions to satisfy a multiplicity of constraints are provided along with an extensive database of “recipes”.

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