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 1H-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.
REUTENS A T, PRENTICE L, ATKINS R C. Epidemiology of diabetic kidney disease. [J]. Med Clin North Am, 2013, 97(1):1-18.
[2]
JIN S X, JIN S, LI X Y, et al. Preparation and in vivo evaluation of glycgrrhizin acid-sodium deoxycholate/phospholipid-mixed micelles[J]. Chin Pharm J(�й�ҩѧ��־), 2013, 48(4):280-285.
[3]
MIN H, SHEN C, SHEN B D, et al. Optimization of glycyrrhizic acid bile salt/phospholipid mixed micelles fast dissolving sublingual films by response surface method[J]. Chin Tradit Herb Drugs(�в�ҩ), 2014, 45(24):3543-3548.
[4]
ZHANG J Z, JING L, HOU S Z, et al. Effect of glycyrrhizic acid on the expression of TGF-��1 in the kidney of the rats with diabetes[J]. Chin J Clin Pharmacol(�й��ٴ�ҩ��ѧ��־), 2010, 26(9):673-676.
[5]
TAN S, LI X, GUO Y, et al. Lipid-enveloped hybrid nanoparticles for drug delivery[J]. Nanoscale, 2013, 5(3):860-872.
[6]
YUAN Z, ZHANG Z R, ZHU D, et al. Specific renal uptake of randomly 50% N-acetylated low molecular weight chitosan[J]. Mol Pharm, 2009, 6(1):305-314.
[7]
WANG X, DU Y, FAN L, et al. Chitosan-metal complexes as antimicrobial agent:synthesis, characterization and structure-activity study[J]. Polymer Bull, 2005, 55(1-2):105-113.
[8]
CHENG M, GAO X, WANG, et al. Synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and its inhibition of liver cancer characteristics in vitro and in vivo[J]. Marine Drugs, 2013, 11(9):3517-3536.
[9]
LIANG N, SUN S, LI X, et al. ��-Tocopherol succinate-modified chitosan as a micellar delivery system for paclitaxel: preparation, characterization and in vitro/in vivo evaluations[J]. Int J Pharm, 2012, 423(2):480-488.
[10]
XIA-KAI H, ZHI-XIANG, XIAO-JUAN W, et al. Low molecular weight hydroxyethyl chitosan-prednisolone conjugate for renal targeting therapy:synthesis, characterization and in vivo studies [J]. Theranostics, 2012, 2(11):1054-1063.
2017, Vol. 52 
