Syntheses of click PEG-dexamethasone conjugates for the treatment of rheumatoid arthritis.
Syntheses of click PEG-dexamethasone conjugates for the treatment of rheumatoid arthritis.
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DOI：
10.1021/bm100578c
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发表时间：
2010-10-11
影响因子：
6.2
通讯作者：
Wang, Dong
中科院分区：
文献类型：
--
作者：
Liu, Xin-Ming;Quan, Ling-dong;Tian, Jun;Laquer, Frederic C.;Ciborowski, Pawel;Wang, Dong
采用Cu（I）催化Huisgen 1，3-偶极环加成反应合成了一种新型的多功能聚乙二醇（PEG）-地塞米松（Dex）线性偶联物（click PEG-Dex）。Dex通过酸不稳定的腙键与点击PEG缀合，以允许药物在病理生理环境中释放。为了评估点击PEG作为多功能药物递送平台的潜力，在佐剂诱导的关节炎（AA）大鼠模型中测试点击PEG-Dex缀合物。体内光学成像数据证实了缀合物在关节炎大鼠中的向关节性。长期治疗研究显示，单次点击PEG-Dex缀合物施用为AA大鼠提供踝关节炎症的持续（> 15天）改善。使用等效剂量的地塞米松磷酸钠（游离Dex）治疗仅提供关节炎的暂时缓解，关节炎在停药后复发。来自点击PEG-Dex和游离Dex治疗组的踝关节之间的进一步组织学和骨矿物质密度比较证实了新型聚合物-药物缀合物的上级抗炎和疾病改善作用。
A novel linear multifunctional polyethylene glycol (PEG)-dexamethasone (Dex) conjugate (click PEG-Dex) was synthesized using facile Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (a click reaction). Dex was conjugated to the click PEG via an acid-labile hydrazone bond to allow the drug release in pathophysiological environment. To evaluate click PEG’s potential as a versatile drug delivery platform, the click PEG-Dex conjugates were tested in an adjuvant-induced arthritis (AA) rat model. In vivo optical imaging data confirmed the arthrotropism of the conjugates in the arthritic rats. Long-term treatment study revealed that a single click PEG-Dex conjugate administration provided sustained (> 15 days) amelioration of ankle joint inflammation to the AA rats. Treatment with equivalent dose of dexamethasone phosphate sodium (free Dex) only provides temporal resolution of the arthritis, which recurred upon treatment withdrawal. Further histological and bone mineral density comparison between the ankle joints from both click PEG-Dex and free Dex treatment groups confirmed the superior anti-inflammatory and disease modifying effects of the novel polymer-drug conjugates.
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影响因子：
4.7
作者：
Pechar, M;Ulbrich, K;Schacht, EH
通讯作者：
Schacht, EH
影响因子：
4.9
作者：
Wang D;Miller SC;Liu XM;Anderson B;Wang XS;Goldring SR
通讯作者：
Goldring SR
影响因子：
--
作者：
CHANG, YH;PEARSON, CM;ABE, C
通讯作者：
ABE, C
影响因子：
6.2
作者：
Liu, Xin-Ming;Thakur, Ashish;Wang, Dong
通讯作者：
Wang, Dong
DOI：
10.1073/pnas.0707090104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Baskin, Jeremy M.;Prescher, Jennifer A.;Bertozzi, Carolyn R.
通讯作者：
Bertozzi, Carolyn R.