β-cyclodextrin polymers as cholesterol sequestrating agents

Abstract

Summary

Elevated serum cholesterol blood levels is one of the central risk factors for cardiovascular diseases. Lowering blood cholesterol have significant impact on lowering cardiovascular disease events. Inhibiting cholesterol absorption in small intestine can significantly lower serum cholesterol levels and thereby - lower cardiovascular events. Β-cyclodextrin (βCD)-dextran polymer is expected to form complexes with cholesterol and avoid absorption together with complexed cholesterol. In this thesis, we investigated βCD-dextran polymers ability to complexate cholesterol in simulation of gastric fluids. βCD-dextran polymer tablets at βCD conc. of 2.5mM complexed 0.0513 mg/ml crystalline cholesterol after 240 minutes in simulation of gastric fluids, while MβCD at conc. of 10mM complexed 0.45 mg/ml crystalline cholesterol. Extrapolated results to 10mM of βCD cons. shows that βCD-dextran polymer is capable of complexing significant amount of cholesterol. βCD-dextran polymer was successfully compressed into tablets with no visible defects of friability during handling. βCD-dextran polymer tablets sequestrate comparable amounts of food cholesterol, compared to experiments with crystalline cholesterol.

Extrapolated results to physiological volumes of gastric fluids shows that βCD-dextran tablets corresponding to a concentration of βCD units of 10 mM were able to solubilize approx. 215 mg of crystalline cholesterol, and approx. 135 mg of food cholesterol after 240 minutes.

Conclusion In simulation of gastric fluids, βCD-dextran polymer tablet can complex approximately 48% of cholesterol in comparison to cholesterol solubilized by MβCD powder. βCD-dextran polymer tablets show ability to complex similar and significant amounts of both crystalline and food cholesterol in simulation of gastric fluids. βCD-dextran polymer shows good compaction properties and were successfully compressed into tablets with no visible defects and no visible friability during handling.