Local release of dexamethasone from polymer millirods effectively prevents fibrosis after radiofrequency ablation
Local release of dexamethasone from polymer millirods effectively prevents fibrosis after radiofrequency ablation
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DOI：
10.1002/jbm.a.30516
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发表时间：
2006-01-01
影响因子：
4.9
通讯作者：
Gao, JM
中科院分区：
文献类型：
--
作者：
Blanco, E;Weinberg, BD;Gao, JM
最近的研究表明，射频（RF）消融后，在消融边界发生纤维化，阻碍抗癌药物从局部植入的聚合物贮库运输到肿瘤复发的消融边缘。本研究的目的是调查策略，可以有效地提供地塞米松（DEX），抗炎剂，以防止纤维化。由聚（D，L-丙交酯-共-乙交酯）（PLGA）组成的聚合物毫杆装载有与羟丙基β-环糊精（HP β-CD）复合的DEX或NaCl和DEX混合物。体外释放研究表明，与含有NaCl和DEX的毫杆相比，与HP β-CD复合的DEX在4天后释放95%的药物，而释放14%。大鼠肝脏经历RF消融并接受DEX-HP β-CD负载的毫杆、PLGA毫杆和腹膜内（i. p.）DEX注射液，或对照PLGA millirods单独。在体内8天后，在对照实验和接受DEX注射的实验中均可以观察到增强的炎症和明确的纤维囊的出现（厚度分别为0.29 +/-0.08和0.26 +/-0.07 mm），在接受DEX毫杆的肝脏中存在最小的炎症和纤维化（0.04 +/-0.01 mm）。这项研究的结果表明，局部释放DEX比全身性腹膜内注射更有效地预防纤维化。(c)2005 Wiley Periodicals，Inc.
Recent studies show that after radiofrequency (RF) ablation, fibrosis occurs at the ablation boundary, hindering anticancer drug transport from a locally implanted polymer depot to the ablation margin, where tumors recur. The purpose of this study is to investigate strategies that can effectively deliver dexamethasone (DEX), an anti-inflammatory agent, to prevent fibrosis. Polymer millirods consisting of poly(D,L-lactide-co-glycolide) (PLGA) were loaded with either DEX complexed with hydroxypropyl P-cyclodextrin (HP beta-CD), or an NaCl and DEX mixture. hi vitro release studies show that DEX complexed with HP beta-CD released 95% of the drug after 4 days, compared to 14% from millirods containing NaCl and DEX. Rat livers underwent RF ablation and received either DEX-HP beta-CD-loaded millirods, PLGA millirods with an intraperitoneal (i.p.) DEX injection, or control PLGA millirods alone. After 8 days iii vivo, heightened inflammation and the appearance of a well-defined fibrous capsule can be observed in both the control experiments and those receiving a DEX injection (0.29 +/- 0.08 and 0.26 +/- 0.07 mm in thickness, respectively), with minimal inflammation and fibrosis present in livers receiving DEX millirods (0.04 +/- 0.01 mm). Results from this study show that local release of DEX prevents fibrosis more effectively than a systemic i.p. injection. (c) 2005 Wiley Periodicals, Inc.