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Updated: Sep 11, 2025
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Microwave-assisted Functionalization of Polyethylene glycol and On-resin Peptides for Use in Chain Polymerizations and Hydrogel Formation
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End group chemistry modulates physical properties and biomolecule release from biodegradable polyesters
Matthew A Borrelli1,2, Jordan J P Warunek3,4,5, Tarini Ravikumar6
1Department of Chemical and Petroleum Engineering, University of Pittsburgh, PA 15261, USA.
Journal of Materials Chemistry. B
|August 11, 2025
Summary
Poly(lactic-co-glycolic acid) (PLGA) microparticle terminal group chemistry significantly impacts protein therapeutic release. Amine-terminated PLGA (PLGA-NH2) microparticles show faster degradation and enhanced drug release, offering new control over long-acting injectables.
Area of Science:
- Biomaterials Science
- Pharmaceutical Sciences
- Polymer Chemistry
Background:
- Long-acting injectable protein therapeutics utilize poly(lactic-co-glycolic acid) (PLGA) microparticles (MP) for controlled release and stability.
- Current models of PLGA MP degradation and erosion do not fully explain drug release kinetics, potentially due to polymer terminal group interactions.
- The availability of functionalized PLGA polymers with varied terminal group chemistries necessitates investigation into their impact on physical properties and drug release.
Purpose of the Study:
- To investigate how different poly(lactic-co-glycolic acid) (PLGA) terminal group chemistries influence polymer physical properties.
- To determine the effect of PLGA terminal group chemistry on the release kinetics of charged biomolecules from microparticles.
- To provide insights for optimizing PLGA microparticle formulations for protein therapeutics.
Main Methods:
- Synthesis and characterization of poly(lactic-co-glycolic acid) (PLGA) microparticles with hydroxyl (PLGA-OH), amine (PLGA-NH2), and carboxylic acid (PLGA-COOH) terminal groups.
- Assessment of polymer physical properties including hydrophobicity, degradation rate, emulsion stability, and phagocytic clearance.
- In vitro release studies of charged biomolecules from the prepared PLGA microparticles.
Main Results:
- Poly(lactic-co-glycolic acid) (PLGA)-amine (PLGA-NH2) exhibited reduced hydrophobicity, faster degradation, emulsion stabilization, and decreased phagocytic uptake.
- Charged biomolecule release rates were accelerated from PLGA-NH2 microparticles and slightly from PLGA-OH microparticles compared to PLGA-COOH.
- Terminal group chemistry significantly alters PLGA microparticle characteristics and drug release profiles.
Conclusions:
- Poly(lactic-co-glycolic acid) (PLGA) terminal group chemistry is a critical factor influencing microparticle properties and drug release kinetics.
- Functionalized PLGA polymers offer tunable characteristics for controlling the release of protein therapeutics.
- Understanding these interactions can lead to improved design of long-acting injectable formulations.
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