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

Morphology, structure, and performance of resulting films can be controlled using unique properties of the electrospray.

Thin films of controlled morphology were fabricated by electrospray drying a colloidal nanoparticle suspension using a conductive and volatile solvent and impacting the nanoparticles on a substrate. Three parameters were used for control: impact velocity, size of the nanoparticles or nanoparticle agglomerates, and solvent volatility. The impact velocity was controlled by charging nanoparticles through electrospray dispersion and varying the electric field driving the particle impaction. It was found that the structure is governed by the relative importance of charged particle drift imposed by the external electric field and the thermal velocity due to Brownian motion. Peclet number correlates with the morphology of the deposit where columnar structures result from high Pe, corresponding to ballistic deposition and porous, fractal-like structures result from small Pe. These patterns match predictions based on Monte Carlo simulations in the literature. For dispersions with higher nanoparticle concentrations, droplet evaporation causes densification of the particle ensemble to form a spherical aggregate that deposits in a predominantly ballistic manner, with smaller aggregates forming denser films. If the droplet evaporation lifetime is altered for the aggregates to be partially wet upon impacting the substrate, the subsequent rapid evaporation of the remaining solvent on the substrate leads to formation of films with high interconnectivity. Films formed by the electrospray technique have large-scale uniformity and their structure is independent of thickness. The interpretation of the observed morphologies in terms of Peclet number and Damkh€ oler number provides a conceptual framework for a rational design of film structures as required by many applications.