Abstract
Protein encapsulation technologies of polymeric microspheres currently in use have been optimized to effectively protect their “protein cargo” from inactivation occurring in biological environments, preserving its bioactivity during release up to several weeks. The scenario of protein delivery would greatly benefit by strategies enabling the production of non-spherical particles. Herein we report an easy and effective stamp-based method to produce poly-lactic-glycolic-acid (PLGA) microparticles encapsulating Vascular Endothelial Growth Factor (VEGF) of different shapes. We demonstrate that PLGA microspheres can be deformed at room temperature exploiting solvent/non-solvent plasticization in order to preserve the properties of the starting microspheres. This gentle method allows the production of shaped particles that provide a prolonged release of VEGF in active form, as verified by an angiogenic assay. The retention of the biological activity of an extremely labile molecule, i.e. VEGF, lets us hypothesize that a wide variety of drug and protein encapsulated polymeric microspheres can be processed using this method.
Highlights
Various ab initio methods to produce microparticles with complex shapes have been described[12,24,25,26,27,28] but, considering the expertise already available for spherical particle technology, the use of microspheres as a starting material to obtain microparticles with different shapes is attractive
As reported in the Methods section, Nile Red (NR)-loaded PLGA microspheres were placed inside the cavities of an elastomeric mold, exposed to a solvent/non-solvent vapor mixture, i.e. dimethylcarbonate (DMC) and Ethanol (EtOH), respectively, and demolded (Fig. 1a,b)
We propose a new and effective method to produce non-spherical polymeric particles starting from previously fabricated PLGA microspheres loaded with Vascular Endothelial Growth Factor (VEGF)/Hp/bovine serum albumin (BSA) exploiting solvent/non-solvent plasticization at room temperature using a vapor mixture
Summary
Various ab initio methods to produce microparticles with complex shapes have been described[12,24,25,26,27,28] but, considering the expertise already available for spherical particle technology, the use of microspheres as a starting material to obtain microparticles with different shapes is attractive. Driven by the willingness to better exploit the advantages related to the use of microspheres as a starting material, and considering the possible effects of liquefaction, the aim of this study was to develop a novel stamp-based technique to produce shaped and isolated microparticles by deforming previously fabricated microspheres under gentle process conditions, i.e. at room temperature using a solvent/non-solvent vapor mixture, and to assess the release of VEGF in active form from the shaped microparticles over time
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