Elena Barbero Colmenar

MONODISPERSE POLYMERIC MICRO AND NANOPARTICLES BY ELECTROSPRAY TECHNOLOGIES

This thesis is focused on different approaches to produce homogeneously-sized polymer-containing particles by electrospray-based technologies. Because of its unique feature of producing very small and quasi-monodispersed particles without agglomeration, electrospray is attracting much interest in different research and application fields, such as biomedical and pharmaceutical. In our first study (Chapter-2), we developed a new methodology to determine the initial droplet size, when electrospraying polymer solutions, from the particles’ volumes analyzed by atomic force microscopy (AFM) after thermal annealing. This was complemented with a particle-morphology electron-microscopy study. In our second and third studies, we produced size-monodisperse polymer/model-drug particles of polyvinylpyrrolidone (PVP) and curcumin (CUR) (Chapter-3), and chitosan submicron particles (Chapter-4), by avoiding unstable modes and corona discharges, and studied the particles size and morphology as a function of the composition and the process variables. In the first case, the most notable effect was the shift from corrugated to smooth-spherical particle morphology for solutions with a higher PVP:CUR ratio, when the RH was increased. In the case of chitosan, a similar effect was observed, although for much smaller particles. In our fourth study (Chapter-5), we prepared monodisperse-globular polymeric particles by avoiding Coulombic instabilities of the electrospray droplets, by exposing them to gas-phase ions of opposite polarity produced by a corona discharge. We demonstrated this method with three different polymer solutions (with PS, CUR-PVP, and chitosan as solutes). The discharged droplets were extracted and collected as solid globular particles on filters. Lastly, in our fifth study (Chapter-6), we combined electrospray with supercritical carbon dioxide (SC-CO2) technologies to produce poly(lactic-co-glycolic acid) (PLGA) nanoparticles (100-200 nm), at a much higher throughput than is possible with conventional electrospray. Here, we studied how size and morphology are affected by the PLGA concentration and the process parameters.

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