Biodegradation of poly(anhydride-esters) into non-steroidal anti-inflammatory drugs and their effect on Pseudomonas aeruginosa biofilms in vitro and on the foreign-body response in vivo
Biodegradation of poly(anhydride-esters) into non-steroidal anti-inflammatory drugs and their effect on Pseudomonas aeruginosa biofilms in vitro and on the foreign-body response in vivo
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DOI：
10.1016/j.biomaterials.2006.05.034
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发表时间：
2006-10-01
期刊：
影响因子：
14
通讯作者：
Uhrich, Kathryn
中科院分区：
文献类型：
--
作者：
Bryers, James D.;Jarvis, Rebecca A.;Uhrich, Kathryn
分别在体外和体内研究了生物降解为水杨酸和己二酸的非甾体抗炎药组成的聚酸酐酯对铜绿假单胞菌定植的抑制作用及其对异物反应的影响。浓度达300 mg/L的SA对铜绿假单胞菌的生长和活力无明显影响，表明SA对铜绿假单胞菌无直接毒性作用。与在无菌介质中的聚合物降解率相比，在活跃生长的细菌培养物存在的情况下，基于水杨酸盐的聚合物的批量降解率仅略有增加(14%)。搅拌间歇系统中的短期(3小时)细菌黏附研究表明，与在生物降解时不释放SA的对照聚合物相比，铜绿假单胞菌的黏附率降低了47%。长期(3天)的生物膜积累研究表明，与对照组相比，水杨酸酯类聚合物的生物膜形成显著减少。利用重组铜绿假单胞菌pMHLAS，在LAS调节子之前含有一个荧光报告基因，以确定基于水杨酸盐的聚合物是否通过释放的SA抑制群体感应通路来阻止生物膜的形成。对铜绿假单胞菌pMHLAS的长期生物膜积累研究暗示，以水杨酸盐为基础的聚合物通过抑制LAS群体感应系统来防止生物膜积累。此外，与对照聚合物不同，基于水杨酸盐的聚合物植入皮下4周可抵抗细胞介导的降解，并保持完好。组织学和免疫组织化学分析表明，水杨酸基聚合物植入物区域的巨噬细胞总体包裹性和稀缺性减少。(C)2006爱思唯尔有限公司。保留所有权利。
The ability of poly(anhydride-esters) composed of non-steroidal anti-inflammatory drugs that biodegrade to salicylic acid (SA) and adipic acid to prevent colonization by Pseudomonas aeruginosa and their effects on the foreign-body response were studied in vitro and in vivo, respectively. Soluble SA in bacterial medium at concentrations up to 300mg/L did not affect the growth rate or viability of P. aeruginosa, indicating that SA does not exhibit a direct toxicity effect on the bacterium. Batch degradation rates of the salicylate-based polymer in the presence of an actively growing bacterial culture only marginally (14%) increased relative to polymer degradation rates in sterile medium. Short-term (3 h) bacterial adhesion studies in agitated batch systems indicated a 47% reduction in the rate of P. aeruginosa adhesion relative to a control polymer that does not release SA upon biodegradation. Long-term (3-day) biofilm accumulation studies indicated a dramatic reduction in biofilm formation on salicylate-based polymer versus controls. A recombinant P. aeruginosa pMHLAS, containing a fluorescent reporter gene prior to the las regulon, was employed to determine whether salicylate-based polymer prevents biofilm formation by the released SA inhibiting quorum sensing pathways. Long-term biofilm accumulation studies with P. aeruginosa pMHLAS insinuate that salicylate-based-polymer prevents biofilm accumulation by inhibiting the las quorum sensing system. Furthermore, unlike control polymer, salicylate-based polymer implanted subcutaneously for a period of 4 weeks-resisted cell-mediated degradation and remained intact. Histological and immunohistochemical analysis indicated a reduction in overall encapsulation and paucity of macrophages in the area of the salicylate-based polymer implant. (c) 2006 Elsevier Ltd. All rights reserved.