Synthesis and evaluation of a well-defined HPMA copolymer-dexamethasone conjugate for effective treatment of rheumatoid arthritis.
Synthesis and evaluation of a well-defined HPMA copolymer-dexamethasone conjugate for effective treatment of rheumatoid arthritis.
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DOI：
10.1007/s11095-008-9683-3
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发表时间：
2008-12
影响因子：
3.7
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;Alnouti, Yazen;Fu, Kai;Thiele, Geoffrey M.;Wang, Dong
目的：研制一种pH敏感的含地塞米松（Dex）的N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物偶联物，用于改善类风湿关节炎（RA）的治疗。合成了一种新的pH敏感性含Dex单体（MA-Gly-Gly-NHN=Dex），并与HPMA进行了可逆加成-断裂转移（RAFT）聚合。分析了HPMA共聚物-Dex偶联物（P-Dex）的结构，并评价了其对佐剂诱导的关节炎（AIA）大鼠的治疗效果。合成了分子量和多分散指数可控的P-Dex。Dex含量可以通过MA-Gly-Gly-NHN=Dex的进料比来控制。用于体外和体内评价的P-Dex的重均分子量（Mw）为34 kDa，PDI为1.34。体外药物释放研究表明，从共轭物的地塞米松释放触发低pH值。临床测量，终点骨矿物质密度（BMD）测试和组织学分级从体内评价都表明，新合成的P-Dex具有强大的和持久的抗炎和关节保护作用。合成了一种具有明确结构的HPMA共聚物-地塞米松偶联物，并证明其是一种有效的抗关节炎治疗剂。在治疗类风湿性关节炎方面可能有独特的临床应用。
To develop a pH-sensitive dexamethasone (Dex)-containing N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugate with well-defined structure for the improved treatment of rheumatoid arthritis (RA). A new pH-sensitive Dex-containing monomer (MA-Gly-Gly-NHN=Dex) was synthesized and copolymerized with HPMA using reversible addition-fragmentation transfer (RAFT) polymerization. The structure of the resulting HPMA copolymer-Dex conjugate (P-Dex) was analyzed and its therapeutic efficacy was evaluated on adjuvant-induced arthritis (AIA) rats. P-Dex was synthesized with controllable molecular weight and polydispersity index (PDI). The Dex content can be controlled by the feed-in ratio of MA-Gly-Gly-NHN=Dex. The P-Dex used for in vitro and in vivo evaluation has a weight average molecular weight (Mw) of 34 kDa and a PDI of 1.34. The in vitro drug-release studies showed that the Dex release from the conjugate was triggered by low pH. Clinical measurements, endpoint bone mineral density (BMD) test and histology grading from the in vivo evaluation all suggest that newly synthesized P-Dex has strong and long-lasting anti-inflammatory and joint protection effects. A HPMA copolymer-dexamethasone conjugate with a well-defined structure has been synthesized and proved to be an effective anti-arthritis therapy. It may have a unique clinical application in the treatment of rheumatoid arthritis.
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影响因子：
--
作者：
CHANG, YH;PEARSON, CM;ABE, C
通讯作者：
ABE, C
影响因子：
3.9
作者：
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通讯作者：
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影响因子：
3.6
作者：
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通讯作者：
KRAUSE, JG
影响因子：
6.2
作者：
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通讯作者：
Santavirta, S
影响因子：
--
作者：
Avnir, Yuval;Ulmansky, Rina;Naparstek, Yaakov
通讯作者：
Naparstek, Yaakov