Pegylation enhances protein stability during encapsulation in PLGA microspheres

Area of Science:

• Biomaterials Science
• Protein Chemistry
• Drug Delivery Systems

Background:

• Protein encapsulation in biodegradable microspheres often leads to denaturation and aggregation.
• Incomplete in vitro protein release from microspheres is a significant challenge in drug delivery.

Purpose of the Study:

• To investigate if pegylation of proteins can enhance their stability during encapsulation in biodegradable microspheres.
• To improve the in vitro release profile of proteins from microspheres.

Main Methods:

• Lysozyme was conjugated with methoxy polyethylene glycol (mPEG).
• Pegylated lysozyme (Lys-mPEG) was characterized using SDS-PAGE, SE-HPLC, and MALDI-TOF mass spectroscopy.
• Stability and release profiles of native and pegylated lysozyme from PLGA microspheres were compared.

Main Results:

• Pegylation of lysozyme with mPEG resulted in a mixture of pegylated isomers with retained specific activity.
• Pegylated lysozyme showed enhanced stability against organic solvents and homogenization, with reduced adsorption to microspheres.
• Native lysozyme exhibited poor release (50% initial, 10% sustained), while Lys-mPEG showed a triphasic, near-complete release over 83 days.

Conclusions:

• Protein pegylation offers substantial protection against destabilization during microsphere encapsulation.
• Pegylated proteins demonstrate improved stability and controlled release profiles from biodegradable microspheres.
• This strategy holds promise for enhancing the efficacy of protein-based therapeutics delivered via microspheres.