Stable cationic microparticles for enhanced model antigen delivery to dendritic cells

Area of Science:

• Biomaterials Science
• Nanotechnology
• Immunology

Background:

• Biodegradable microparticles are crucial for drug and protein delivery.
• Surface properties of microparticles influence cellular interactions, including phagocytosis and immune cell activation.
• Poly(lactic-co-glycolic acid) [PLGA] is a widely used biodegradable polymer for microparticle fabrication.

Purpose of the Study:

• To prepare physically stable cationic microparticles for protein delivery.
• To investigate the impact of microparticle surface properties on phagocytosis by dendritic cells (DCs).
• To evaluate the effect of microparticle surface modification on DC phenotype and function.

Main Methods:

• Fabrication of protein-loaded PLGA microparticles using a micromixer-based w/o/w solvent evaporation method.
• Surface modification of microparticles using anionic (polyvinyl alcohol) and cationic (cetyltrimethylammonium bromide, chitosan, DEAE-dextran) agents.
• Assessment of microparticle stability, charge, and cell toxicity.
• Phagocytosis studies using human monocytes and monocyte-derived DCs analyzed by flow cytometry.

Main Results:

• Chitosan and DEAE-dextran modifications yielded stable cationic microparticles without observed cell toxicity.
• Cetyltrimethylammonium bromide modification led to particle aggregation and charge loss.
• Phagocytosis of anionic and cationic microparticles did not induce DC maturation markers due to low endotoxin levels.
• DEAE-dextran modified microparticles demonstrated enhanced model protein delivery into phagocytic cells.

Conclusions:

• Stable, biodegradable PLGA microparticles can be prepared with tunable surface properties for protein delivery.
• DEAE-dextran modified microparticles are promising for targeted protein delivery to phagocytic cells like DCs.
• These microparticles hold potential for applications in DC-based cell therapies.