Protein loaded biodegradable microspheres based on PLGA-protein bioconjugates

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Chemistry

Background:

• Biodegradable polymers like poly(D,L-lactic-co-glycolic acid) (PLGA) are crucial for controlled drug release.
• Protein drug instability during formulation remains a significant challenge in developing effective delivery systems.
• Lysozyme serves as a model protein drug for evaluating formulation strategies.

Purpose of the Study:

• To chemically conjugate lysozyme to PLGA to create a stable drug-carrier conjugate.
• To formulate PLGA-lysozyme microspheres using a single emulsion solvent evaporation technique.
• To investigate the impact of conjugation on microsphere morphology, loading efficiency, and protein release behavior.

Main Methods:

• Chemical conjugation of PLGA (terminal carboxylic acid) to lysozyme (amine groups) using carbodiimide in dimethylsulphoxide (DMSO).
• Microsphere preparation via oil-in-water (O/W) single emulsion solvent evaporation of the PLGA-lysozyme conjugate.
• Comparative analysis of microsphere characteristics (morphology, loading, release) against formulations with unconjugated lysozyme using O/W single and water-in-oil-water (W/O/W) double emulsion methods.

Main Results:

• Successful chemical conjugation of PLGA to lysozyme was achieved.
• The O/W single emulsion method with the PLGA-lysozyme conjugate yielded microspheres with specific morphological characteristics.
• Protein release profiles and stability were evaluated, highlighting improvements compared to formulations with unconjugated lysozyme.

Conclusions:

• Chemical conjugation of lysozyme to PLGA offers a viable strategy to enhance protein stability in microsphere formulations.
• The O/W single emulsion solvent evaporation technique is suitable for preparing PLGA-lysozyme microspheres.
• This approach holds promise for improving the delivery of protein-based therapeutics.