Cationic Polysaccharides Bind to the Endothelial Cell Surface Extracellular Matrix Involving Heparan Sulfate.

Area of Science:

• Biomaterials Science
• Cell Biology
• Drug Delivery Systems

Background:

• Cationic polysaccharides are explored for bloodstream drug delivery, but clinical translation is limited.
• The endothelial glycocalyx, an anionic extracellular matrix, influences interactions with charged molecules.
• Understanding polysaccharide interactions with the glycocalyx is crucial for effective drug delivery.

Purpose of the Study:

• To investigate the interaction between charged polysaccharides and the endothelial glycocalyx.
• To determine how polysaccharide charge affects association with the glycocalyx and its components.
• To elucidate the mechanism of interaction and its functional consequences for drug delivery.

Main Methods:

• Comparison of poly(acetyl, arginyl) glucosamine (PAAG), dextran, and hyaluronan association with an in vitro glycocalyx model.
• Assessment of polysaccharide binding to heparan sulfate (HS) within the glycocalyx.
• Mechanistic studies on PAAG-HS interaction, including charge-based association and protection from degradation.

Main Results:

• PAAG demonstrated the highest association with the endothelial glycocalyx, followed by neutral dextran and anionic hyaluronan.
• PAAG specifically binds to heparan sulfate (HS) in the glycocalyx, promoting intracellular accumulation.
• A charge-dependent association of polysaccharides with HS was observed.
• PAAG binding to HS occurs via condensation and protects HS from degradation.

Conclusions:

• Polysaccharide charge is a key determinant of interaction with the endothelial glycocalyx.
• PAAG's specific binding to HS offers a mechanism for enhanced cellular uptake and potential drug delivery applications.
• Understanding these interactions can guide the design of improved polysaccharide-based drug delivery systems.