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
