甘草酸-低分子壳聚糖偶联物大鼠体内组织分布研究

目的：研究甘草酸-低分子壳聚糖（GA-LMWC）偶联物在大鼠体内组织分布特征，探讨GA-LMWC偶联物作为肾靶向药物的可行性。方法：将甘草酸溶液和GA-LMWC偶联物溶液分别经尾静脉注射按剂量10 mg·kg^-1给予SD大鼠，并于给药后1，4，8 h取各组织（心、肝、脾、肺、肾），采用HPLC测定各组织（心、肝、脾、肺、肾）中甘草酸的含量。结果：大鼠尾静脉注射GA-LMWC偶联物后1，4，8 h在肾脏中的分布较甘草酸组显著提高，分别为甘草酸组的1.34倍（P<0.05）、1.46倍（P<0.001）和2.83倍（P<0.01）；在肝脏和脾脏的分布较甘草酸组显著降低（P<0.01）。结论：与游离甘草酸相比，GA-LMWC偶联物改变了甘草酸大鼠体内分布特征，显著增加了GA在肾脏的分布，延长了其肾脏滞留时间，增强了甘草酸的肾脏靶向性。

Tissue distribution of glycyrrhizic acid-low molecular weight chitosan conjugates in rats

OBJECTIVE To investigate the tissue distribution of glycyrrhizic acid-low molecular weight chitosan conjugates (GA-LMWC) in rats and to explore the feasibility of using GA-LMWC as a kidney-targeting drug delivery system. METHODS The concentrations of glycyrrhizic acid in heart, liver, spleen, lung and kidney of rats were determined by HPLC method after intravenous administration of 10 mg·kg^-1 of GA or GA-LMWC at 1, 4, 8 h, respectively. RESULTS The tissue distribution of GA-LMWC was different from that of free GA. In kidney, the concentration of GA from GA-LMWC was significantly increased compared to GA group by 1.34-fold (P<0.05), 1.46-fold (P<0.001), and 2.83-fold (P<0.01) as that of GA after intravenous administration at 1, 4, 8 h, respectively. Meanwhile the distributions of GA from GA-LMWC in liver and spleen decreased significantly (P<0.01) compared to GA group. CONCLUSION These results demonstrate that the distribution of GA is changed by the conjugates, which increases the distribution of GA in kidney significantly, prolongs the retention time of the kidney, and indicate that the GA-LMWC conjugates is potential as a kidney targeting drug delivery system.