PLGA based formulations with poly(2-oxazoline)s for controlled dexamethasone release from thin extrudates

PLGA is a landmark in polymer-based drug delivery, due to its biocompatibility, biodegradability and great mechanical strength. However, its high mechanical resistance tends to be unfavorable for implantation, as it creates sharp edges upon rupture, which can cause damage to the patient. Adding polyethylene glycol (PEG) as plasticizer reduces stiffness in PLGA blends, however with significant drawbacks due to deformation upon implantation. This motivates our evaluation of poly (2-alkyl-oxazoline)s (POx) as an alternative plasticizer for PLGA, probing its mechanical properties and the release behavior of dexamethasone (Dex) from POx/PLGA-based blends. Poly(2-oxazoline)s with defined chain length bearing different alkyl side chains were synthesized using a microwave assisted living polymerization, and characterized using gel permeation chromatography (GPC) and matrix assisted laser desorption ionization time of flight (MALDI-ToF) mass spectrometry. To achieve a homogeneous distribution of the POx inside the PLGA-polymer blend, polymer powders were cryo-milled and subsequently extruded, creating thin filaments as possible candidates for in vivo implantation. In addition to the in vitro drug release, the mechanical properties of the filaments were studied using melt rheology and texture analysis. Phase separation and micro phase behavior was observed using differential scanning calorimetry (DSC) and wide angle x-ray scattering (WAXS). A favorable plasticizing effect of the poly(2-alkyl-oxazoline)s in the PLGA blends was observed, reducing the lag time and increasing the drug release kinetics. Significant improvements in their mechanical properties prospects their use in future intracochlear implants, especially for the PEtOx containing formulations.