低分子量壳聚糖-泼尼松龙结合物的药效学研究

Study on the pharmacodynamics of low molecular weight chitosan-prednisolone conjugate

目的研究低分子量壳聚糖(LMWC)-泼尼松龙结合物对微小病变肾病模型大鼠的治疗效果。方法选择泼尼松龙作为模型药物,筛选出52.7%乙酰度的低分子量羟乙基壳聚糖(HE-LMWC-53)作为载体材料,通过丁二酸间隔基共价相连,建立了柔红霉素诱导微小病变肾病(MCN)的大鼠模型,通过结合物治疗模型大鼠的药效研究,证明了结合物能有效减轻MCN模型大鼠的肾病综合征,且连续给药20 d,并未观察到明显的骨质疏松等不良反应。结果和结论 LMWC-泼尼松龙结合物能有效地治疗肾病综合征,LMWC是值得广泛应用的肾靶向药物载体。

OBJECTIVE To investigate the therapeutic effect of low molecular weight chitosan-prednisolone conjugate for minimal change nephrosis（MCN） model rats.METHODS In our previous study,low molecular weight chitosan（LMWC） showed the good renal targeting profile and safety.Prednisolone as a model drug,was covalently coupled with 52.7% N-acetylation hydroxyethyl chitosan with low molecular weight（HE-LMWC-53）via a succinic acid spacer.The MCN model rats induced by daunorubicin were established and the pharmacodynamics was carried out to evaluate the therapeutical efficiency of prednislone-HE-LMWC-53 conjugate.The results showed that the induced nephrotic syndrome in MCN rats was effectively relieved and glucocorticoid-induced osteoporosis was not observed in the rats after daily administration for 20 days by iv injection.RESULTS and CONCLUSION Low molecular weight chitosan-prednisolove conjugate is effective for nephrotic syndrome and LMWC is a promising novel carrier for renal targeting.