Synthesis and HK-2 Cellular Uptake of Low Molecular Weight Chitosan Glycyrrhizin Conjugate / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare conjugate of low molecular weight chitosan(LMWC) with glycyrrhizin (GL) and investigate its cellular uptake by proximal tubular epithelial cells (HK-2). METHODS: Glycyrrhizin-LMWC (GL-LMWC) conjugate was synthesized by the reaction between the amino group of LMWC and the active ester group of GL. Drug release was studied in phosphate buffer (pH 4.0) containing papain. The uptake of the conjugate by HK-2 cells and its intracellular distribution was studied with laser confocal microscopy. RESULTS: The chemical structure of GL-LMWC conjugate was confirmed by IR and H-NMR. The GL grafting rate was determined to be 29.3%. The drug liberation from the conjugates was significantly accelerated in the presence of papain, which confirmed the capability of the conjugate to degrade in lysosomes. The conjugate could be internalized by HK-2 cells. CONCLUSION: The GL-LMWC conjugate with well-defined structure is successfully synthesized and exhibitts high cellular uptake efficiency. The conjugate has the potential to retaing GL in the kidney for a prolonged duration and to sustain its release locally for better efficacy.