Low molecular weight hydroxyethyl chitosan-prednisolone conjugate for renal targeting therapy: synthesis, characterization and in vivo studies.
Low molecular weight hydroxyethyl chitosan-prednisolone conjugate for renal targeting therapy: synthesis, characterization and in vivo studies.
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用于肾脏靶向治疗的低分子量羟乙基壳聚糖-泼尼松龙缀合物：合成、表征和体内研究
作者：
He XK;Yuan ZX;Wu XJ;Xu CQ;Li WY
为了进一步评价我们之前开发的低分子量羟乙基壳聚糖（LMWHC）的潜在肾靶向特性，通过EDC/NHS化学将泼尼松龙（Pre）与LMWHC缀合以改善糖皮质激素在体内的治疗效果。将缀合物表示为LMWHC-Pre。通过反相高效液相色谱法（HPLC）与Kromasil C18柱测定结合物中泼尼松龙的含量。结果表明，泼尼松龙与低分子量肝素的偶联度为76.7±3.2 μg·mg-1。研究了LMWHC-Pre在不同条件下的稳定性和理化性质。研究LMWHC-Pre在静脉内（i. v.）给药后，将异硫氰酸荧光素（FITC）偶联至缀合物以探索肾靶向功效。体内实验结果表明，当FITC-LMWHC和泼尼松龙的混合物共同给药时，大量的缀合物积聚到肾脏中，而可以检测到可忽略的信号。LMWHC-Pre的初步药效学研究表明，该偶联物能有效缓解微小病变肾病（MCN）模型大鼠的肾病综合征。毒性研究还显示，在治疗20天后，LMWHC-Pre几乎没有糖皮质激素诱导的骨质疏松症。从这项研究中，LMWHC-Pre可能被用作治疗慢性肾脏疾病的有效潜在候选药物。
To further evaluate the potential renal targeting profile of low molecular weight hydroxyethyl chitosan (LMWHC) we developed before, prednisolone (Pre) was conjugated with LMWHC by EDC/NHS chemistry to improve the therapeutic effect of glucocorticoids in vivo. The conjugate was denoted as LMWHC-Pre. The prednisolone content of the conjugate was determined by reversed-phase high-performance liquid chromatography (HPLC) with Kromasil C18 column. The results showed that the average coupling degree of prednisolone to LMWHC was 76.7±3.2 μg·mg-1. The stability and physicochemical characterization of LMWHC-Pre under various conditions were also investigated. To study the fate of LMWHC-Pre after intravenous (i.v.) administration, fluorescein isothiocyanate (FITC) was coupled to the conjugate to explore the renal targeting efficacy. The in vivo results showed that significant amount of the conjugate was accumulated into the kidneys while negligible signal could be detected when the mixture of FITC-LMWHC and prednisolone was co-administered. The preliminary pharmacodynamics study of LMWHC-Pre showed that the conjugate could effectively alleviate the nephrotic syndrome of rats induced by minimal change nephrosis (MCN) model. Toxicity study also revealed that there was little glucocorticoid-induced osteoporosis by LMWHC-Pre upon 20 days of treatment. From this study, LMWHC-Pre may be employed as an effective potential drug candidate for the treatment of chronic renal disease.
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影响因子：
7.3
作者：
Haverdings, RFG;Haas, M;Moolenaar, F
通讯作者：
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158.5
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GRISSO, JA;KELSEY, JL;KAPLAN, F
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3.8
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影响因子：
14
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