title: 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.
authors.affiliation: Department of Electronic & Electrical Engineering, University College London, London WC1E 7JE, UK.
authors.forename: Salman A
authors.initials: SA
authors.lastname: Malik
authors.affiliation: Department of Electronic & Electrical Engineering, University College London, London WC1E 7JE, UK.
authors.forename: Wing H
authors.initials: WH
authors.lastname: Ng
authors.affiliation: School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: James
authors.initials: J
authors.lastname: Bowen
authors.affiliation: Department of Mechanical Engineering & Materials Science, Yale University, New Haven, CT 06520-8286, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Mechanical Engineering & Materials Science, Yale University, New Haven, CT 06520-8286, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gomez
authors.affiliation: Department of Electronic & Electrical Engineering, University College London, London WC1E 7JE, UK. Electronic address: a.kenyon@ucl.ac.uk.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kenyon
authors.affiliation: Division of Medicine, University College London, London WC1E 6JJ, UK. Electronic address: r.m.day@ucl.ac.uk.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Day
mesh_terms: D003692:Delayed-Action Preparations; D007700:Kinetics; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D012235:Rhodamines / Q000032:analysis*; D013059:Spectrum Analysis, Raman; D013499:Surface Properties; D013818:Thermogravimetry
chemical_list: D003692:Delayed-Action Preparations; D012235:Rhodamines; C026188:rhodamine 6G; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Electrosprays; Microspheres; Poly(lactic-co-glycolic acid) (PLGA); Thermally induced phase separation (TIPS)