Lysozyme microencapsulation within biodegradable PLGA microspheres: urea effect on protein release and stability

Area of Science:

• Biomaterials Science
• Drug Delivery
• Protein Chemistry

Background:

• Protein aggregation and instability are significant challenges in developing encapsulated protein therapeutics.
• Poly(D, L-lactide-co-glycolide) (PLGA) microspheres are widely used for controlled protein drug delivery.
• Understanding protein release mechanisms and stability within PLGA microspheres is crucial for effective formulation.

Purpose of the Study:

• To investigate the effect of urea on lysozyme release kinetics from PLGA microspheres.
• To elucidate the mechanisms underlying urea-enhanced protein release and stability.
• To explore the potential of urea as an excipient for improved protein encapsulation and sustained release.

Main Methods:

• Lysozyme encapsulation in PLGA microspheres using a double emulsion solvent evaporation technique.
• In vitro release studies of lysozyme from PLGA microspheres in the presence of varying urea concentrations.
• Analysis of protein conformation and aggregation state of released lysozyme.

Main Results:

• Lysozyme release rate increased with increasing urea concentration in the incubation medium.
• Urea facilitated lysozyme release by suppressing protein aggregation and promoting diffusion of unfolded protein molecules.
• A urea-based formulation demonstrated a more sustained release profile and reduced dimer formation of released lysozyme, with maintained correct conformation after refolding.

Conclusions:

• Urea can enhance protein release from PLGA microspheres by modulating protein stability and diffusion.
• Utilizing urea as an excipient offers a promising strategy for developing improved formulations of protein-encapsulated PLGA microspheres.
• This research provides valuable insights into protein release mechanisms and stability considerations for biodegradable polymer-based drug delivery systems.