Affinity interactions drive post-implantation drug filling, even in the presence of bacterial biofilm.
Affinity interactions drive post-implantation drug filling, even in the presence of bacterial biofilm.
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DOI：
10.1016/j.actbio.2017.04.015
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发表时间：
2017-07-15
影响因子：
9.7
通讯作者：
von Recum HA
中科院分区：
文献类型：
--
作者：
Cyphert EL;Zuckerman ST;Korley JN;von Recum HA
目前外科手术的术后护理标准（包括器械植入）规定了预防性抗菌治疗，但仍有一定比例的患者发生感染。治疗此类感染所需的全身性抗菌治疗可导致下游组织毒性并产生耐药细菌。为了克服与全身给药相关的问题，已经开发了一种掺入特定药物亲和力的聚合物，其具有在植入后甚至在细菌生物膜存在下用抗菌剂填充或再填充的潜力。该聚合物可用作植入物涂层或独立药物递送装置，并且可转化为多种应用，例如植入或留置医疗装置和/或手术部位感染。在模拟植入后组织条件的体外填充/再填充模型中分析空的基于亲和力的药物递送聚合物的填充。将不存在细菌的情况下的填充与存在不同成熟度的细菌生物膜的情况下的填充进行比较，以证明在体内实验之前必要的概念验证。抗生素填充到生物膜涂覆的亲和聚合物中与在没有生物膜的相同亲和聚合物中观察到的药物填充相当，表明亲和聚合物即使在生物膜存在下也保持用抗生素填充的能力。此外，植入后填充的抗生素在抑菌圈测定中显示出持续的杀菌活性，证明植入后在根除生物膜中的细菌所需的时间范围内递送填充的抗生素的能力。这项工作表明，亲和聚合物可以在植入后填充高水平的抗生素，而不依赖于生物膜的存在，从而在感染的情况下可能使装置挽救而不是移除。
Current post-operative standard of care for surgical procedures, including device implantations, dictates prophylactic antimicrobial therapy, but a percentage of patients still develop infections. Systemic antimicrobial therapy needed to treat such infections can lead to downstream tissue toxicities and generate drug-resistant bacteria. To overcome issues associated with systemic drug administration, a polymer incorporating specific drug affinity has been developed with the potential to be filled or refilled with antimicrobials, post-implantation, even in the presence of bacterial biofilm. This polymer can be used as an implant coating or stand-alone drug delivery device, and can be translated to a variety of applications, such as implanted or indwelling medical devices, and/or surgical site infections. The filling of empty affinity-based drug delivery polymer was analyzed in an in vitro filling/refilling model mimicking post-implantation tissue conditions. Filling in the absence of bacteria was compared to filling in the presence of bacterial biofilms of varying maturity to demonstrate proof-of-concept necessary prior to in vivo experiments. Antibiotic filling into biofilm-coated affinity polymers was comparable to drug filling seen in same affinity polymers without biofilm demonstrating that affinity polymers retain ability to fill with antibiotic even in the presence of biofilm. Additionally, post-implantation filled antibiotics showed sustained bactericidal activity in a zone of inhibition assay demonstrating post-implantation capacity to deliver filled antibiotics in a timeframe necessary to eradicate bacteria in biofilms. This work shows affinity polymers can fill high levels of antibiotics post-implantation independent of biofilm presence potentially enabling device rescue, rather than removal, in case of infection.
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影响因子：
5.6
作者：
Orgaz B;Lobete MM;Puga CH;San Jose C
通讯作者：
San Jose C
肝组织的多模式幻影。
影响因子：
3.7
作者：
Chmarra MK;Hansen R;Mårvik R;Langø T
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Langø T
影响因子：
30.3
作者：
Cohen NR;Lobritz MA;Collins JJ
通讯作者：
Collins JJ
DOI：
10.1023/b:resb.0000040469.26208.83
发表时间：
2003-01-01
期刊：
Reviews in Environmental Science and Bio/Technology
影响因子：
--
作者：
Francolini, I.;Donelli, G.;Stoodley, P.
通讯作者：
Stoodley, P.
DOI：
10.1039/c4tb00083h
发表时间：
2014-05-14
期刊：
Journal of materials chemistry. B
影响因子：
--
作者：
Halpern JM;Gormley CA;Keech M;von Recum HA
通讯作者：
von Recum HA