Electrospray synthesis and properties of hierarchically structured PLGA TIPS microspheres for use as controlled release technologies

Abstract

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.

Disease‐Triggered Drug Release Effectively Prevents Acute Inflammatory Flare‐Ups, Achieving Reduced Dosing

“…Where traditional fabrication methods may suffer from inhomogeneous release profiles and lack batch‐to‐batch reproducibility, our particles manufactured by electrospray resulted in highly reproducible particles with excellent control of size and monodispersity. This is in accordance with other reports using electrospray, showing that electrospray provides a versatile method for particle manufacturing over a wide size range and being applicable to several different polymers, including AcDex . In addition, the particles showed high stability at pH 7.4 over eight days (Figure A–C), indicating that the particles could be used within the suggested eight‐day timeframe.…”

Emulsion Techniques for the Production of Pharmacological Nanoparticles

“…Electrospray is a flow of constant liquid and pressure typically pressed through a needle subjected to high electrical field. Fine droplets are produced and the solvent is evaporated during their move toward the collector . This process is largely influenced and controlled by liquid viscosity, needle diameter, pressure, and distance between needle tip and collector plate.…”

“…Fine droplets are produced and the solvent is evaporated during their move toward the collector. [7] This process is largely influenced and controlled by liquid viscosity, needle diameter, pressure, and dis tance between needle tip and collector plate. Moreover, polymer concentration is also crucial because too large concentrations may produce fibers (electrospinning).…”

An Orthogonal Model to Study the Effect of Electrospraying Parameters on the Morphology of poly (d,l)-lactide-co-glycolide (PLGA) Particles

“…Despite all the advantages associated polymers, such as poly-lactide-co-glycolide (PLGA), polycaprolactone (PCL) etc. has found its biggest applications in biomedical engineering [4][5][6][7] and drug delivery [8][9][10][11][12][13][14]. Despite all the advantages associated with electrospraying, nevertheless, the optimization of the spraying procedure has been based on a time-consuming trial-and-error process.…”