NOVEL STRATEGY TO PRODUCE NON-SPHERICAL POLYMERIC MICROPARTICLES FOR DRUG DELIVERY AND TISSUE ENGINEERING

Abstract

The aim of this study was to develop a general method to produce polymeric particles of non-spherical shape and encapsulating labile biomolecules starting from previously fabricated spherical particles, suitable for applications in the field of drug delivery and tissue engineering. The main concern was not only to preserve the biological activity of such molecules during the production process, but also to provide elaborate particles which could release bioactive moieties over a long time span. To date, this demanding task is only addressed by particles which are spherical in shape. For instance, current protein encapsulation technologies of polymeric microspheres have been optimized for effectively protect their protein cargo from inactivation occurring in biological environments, preserving its bioactivity during release up to several weeks. Nevertheless, the scenario of drug delivery and tissue engineering would be greatly expanded by strategies that enable the production of particles both with complex shape and with the beneficial properties of spherical particles. Therefore, as a proof of principle, it is has been developed an easy and effective stamp-based method to produce poly-lactic-glycolic-acid (PLGA) microparticles encapsulating Vascular Endothelial Growth Factor (VEGF), with different shapes. It has been demonstrated that PLGA microspheres can be deformed at room temperature exploiting solvent/non-solvent plasticization. To predict the depression of the glass transition temperature of the polymer due to solvent sorption, a thermodynamic model and measurements with a quartz crystal microbalance were employed. Since the properties of the starting microspheres are not altered by the process conditions, this gentle method allows to produce shaped particles which 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, let us to hypothesize that a wide variety of drugs and proteins encapsulated in thermoplastic polymers can be processed with this method. It was also demonstrated that this method allows to produce shaped and porous microparticles made of gelatin, which are of great interest in the field of tissue engineering. Furthermore, needle-shaped microparticles for transdermal drug delivery, and sintered microparticles have been produced.