Prevention of postsurgical tissue adhesion by anti-inflammatory drug-loaded Pluronic mixtures with sol-gel transition behavior

Prevention of postsurgical tissue adhesion by anti-inflammatory drug-loaded Pluronic mixtures with sol-gel transition behavior
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DOI:
10.1002/jbm.a.30239
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发表时间:
2005-03-01
影响因子:
4.9
通讯作者:
Lee, JH
Lee, JH
中科院分区:
工程技术3区
文献类型:
--
作者:
Oh, SH;Kim, JK;Lee, JH

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制备了溶胶-凝胶转变温度可控的Pluronic F127/F68混合物,包括轻度交联的藻酸盐和非甾体抗炎药(布洛芬),以评估其作为组织粘附屏障凝胶的潜力。Pluronic混合物的溶胶-凝胶转变温度可以通过调节F127/F68比例和聚合物浓度来控制。温和交联的海藻酸盐具有静止流动性,提供了Pluronic混合物凝胶在体内的停留稳定性。将Iceland装载在Pluronic混合物中以减少体内的炎症反应,从而防止组织粘连。Pluronic混合物的凝胶化温度不受藻酸盐的影响,但通过加入布洛芬而降低。在体外药物释放行为和在体内腹膜组织粘附的普朗尼克混合物的溶胶-凝胶转变刚好低于体温进行了研究。采用无膜溶出模型考察了布洛芬(1重量%)-负载的Pluronic混合物凝胶在37 ℃下的药物释放行为。混合物凝胶中的药物在前7天内连续释放高达总负载量的约45-65%。为了体内评价组织抗粘连潜力,将含/不含药物的Pluronic混合物涂覆在大鼠腹膜壁缺损上,并比较其组织粘连程度和组织反应(炎症反应、肉芽组织形成和器官毒性)。观察到布洛芬对腹膜组织抗粘连具有积极作用。Pluronic F127/F68/藻酸盐/布洛芬混合物凝胶(25重量%的F127/F68 [7/3],1重量%布洛芬)对于预防腹膜组织粘连高度有效,并且显示出相对低的炎症反应和无毒性,因此可以是作为可涂覆或可注射的组织粘连屏障凝胶的良好候选材料。(C)2005 Wiley Periodicals,Inc.
Sol-gel transition temperature-controllable Pluronic F127/F68 mixtures including mildly crosslinked alginate and nonsteroidal anti-inflammatory drug (ibuprofen) were prepared to evaluate their potential as tissue adhesion barrier gels. The sol-gel transition temperatures of the Pluronic mixtures could be controlled by adjusting F127/F68 ratio and polymer concentration. The mildly crosslinked alginate with still flow property provided the residence stability of Pluronic mixture gels in the body. Ibuprofen was loaded in Pluronic mixtures to reduce inflammatory response in the body and, thus, to prevent tissue adhesion. The gelation temperatures of the Pluronic mixtures were not affected by the alginate but lowered by the addition of ibuprofen. The in vitro drug release behavior and in vivo peritoneal tissue adhesion of the Pluronic mixtures with the sol-gel transition just below body temperatures were investigated. The drug release behavior from the ibuprofen (1 wt%)-loaded Pluronic mixture gels at 37degreesC was examined using a membrane-less dissolution model. The drug in the mixture gels was released continuously up to about 45-65% of the total loading amount during the first 7 days. For in vivo evaluation of tissue anti-adhesion potential, the Pluronic mixtures with/without drug were coated on the peritoneal wall defects of rats and their tissue adhesion extents and tissue reactions (inflammatory response, granulation tissue formation, and toxicity in organs) were compared. It was observed that ibuprofen has a positive effect for the peritoneal tissue anti-adhesion. The Pluronic F127/F68/alginate/ibuprofen mixture gel (25 wt% of F127/F68 [7/3], 1 wt% ibuprofen) was highly effective for the prevention of peritoneal tissue adhesion and showed a relatively low inflammatory response and non-toxicity, and thus can be a good candidate material as a coatable or injectable tissue adhesion barrier gel. (C) 2005 Wiley Periodicals, Inc.