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

Philipp S Hilgeroth1,2, Eric Lehner3, Juliana Martins-Schalinski2,4

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Poly(2-alkyl-oxazoline)s (POx) improve poly(lactic-co-glycolic acid) (PLGA) blends for drug delivery. These POx plasticizers enhance mechanical properties and drug release kinetics, showing promise for medical implants.

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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.