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

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Poly(lactic-co-glycolic acid) (PLGA) is a key polymer in drug delivery, but its brittleness limits implantation applications.
• Existing plasticizers like polyethylene glycol (PEG) for PLGA have drawbacks, including deformation upon implantation.
• There is a need for alternative plasticizers to improve PLGA's mechanical properties and drug release profiles.

Purpose of the Study:

• To evaluate poly(2-alkyl-oxazoline)s (POx) as a potential plasticizer for PLGA.
• To investigate the impact of POx on the mechanical properties and dexamethasone release from PLGA blends.
• To explore the suitability of POx/PLGA blends for in vivo implantation, particularly in intracochlear devices.

Main Methods:

• Synthesis and characterization of poly(2-oxazoline)s with varying alkyl side chains using microwave-assisted living polymerization, GPC, and MALDI-ToF.
• Preparation of homogeneous POx/PLGA blends via cryo-milling and extrusion into thin filaments.
• Assessment of mechanical properties (melt rheology, texture analysis), in vitro drug release kinetics, phase behavior (DSC, WAXS).

Main Results:

• Poly(2-alkyl-oxazoline)s demonstrated a favorable plasticizing effect on PLGA blends, reducing stiffness.
• POx incorporation led to reduced lag time and increased drug release kinetics for dexamethasone.
• Formulations containing poly(2-ethyl-oxazoline) (PEtOx) showed significant improvements in mechanical properties.

Conclusions:

• Poly(2-alkyl-oxazoline)s are effective plasticizers for PLGA, enhancing its suitability for drug delivery applications.
• The improved mechanical properties and drug release profiles of POx/PLGA blends suggest potential for intracochlear implants.
• PEtOx-containing POx/PLGA formulations show particular promise for future biomedical device development.