Development of Novel Amphotericin B-Immobilized Nitric Oxide-Releasing Platform for the Prevention of Broad-Spectrum Infections and Thrombosis.
Development of Novel Amphotericin B-Immobilized Nitric Oxide-Releasing Platform for the Prevention of Broad-Spectrum Infections and Thrombosis.
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DOI：
10.1021/acsami.1c01330
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发表时间：
2021-05-05
影响因子：
9.5
通讯作者：
Handa, Hitesh
中科院分区：
文献类型：
--
作者：
Devine, Ryan;Douglass, Megan;Ashcraft, Morgan;Tayag, Nicole;Handa, Hitesh
关键词：
目前用于诊断、监测和治疗患者的留置医疗器械总是会遭受两种常见的临床并发症：广谱感染和器械引起的血栓形成。目前，感染是通过抗生素或抗真菌治疗来控制的，但抗生素耐药性的出现、顽固生物膜的形成以及识别罪魁祸首的困难使得治疗变得越来越具有挑战性。此外，全身抗凝已被用于治疗设备引起的血栓形成，但随后与所有可用疗法相关的危及生命的出血事件需要替代解决方案。在这项研究中，通过两步过程开发了一种广谱抗菌、抗血栓表面，将一氧化氮 (NO) 供体 S-亚硝基-N-乙酰青霉胺 (SNAP) 的掺入与抗真菌两性霉素 B (AmB) 固定在聚二甲基硅氧烷 (PDMS) 上相结合。这种新颖的策略结合了 NO（一种杀菌剂和血小板抑制剂）与 AmB（一种有效的抗真菌剂）的主要优点。我们证明，体外暴露 24 小时后，与对照相比，SNAP-AmB 表面显着降低了粘附的金黄色葡萄球菌 (99.0 ± 0.2%)、大肠杆菌 (89.7 ± 1.0%) 和白色念珠菌 (93.5 ± 4.2%) 的活力。此外，在体外猪血浆暴露 2 小时后，与对照组相比，SNAP-AmB 表面粘附的血小板数量减少了 74.6 ± 3.9%。最后，细胞毒性测定验证了该材料对人类成纤维细胞没有任何细胞毒性副作用。这种新颖的方法首次将抗真菌表面功能化与一氧化氮释放技术相结合，为降低与留置医疗器械相关的广谱感染和血栓形成率迈出了有希望的一步。
Indwelling medical devices currently used to diagnose, monitor, and treat patients invariably suffer from two common clinical complications: broad-spectrum infections and device-induced thrombosis. Currently, infections are managed through antibiotic or antifungal treatment, but the emergence of antibiotic resistance, the formation of recalcitrant biofilms, and difficulty identifying culprit pathogens have made treatment increasingly challenging. Additionally, systemic anticoagulation has been used to manage device-induced thrombosis, but subsequent life-threatening bleeding events associated with all available therapies necessitates alternative solutions. In this study, a broad-spectrum antimicrobial, antithrombotic surface combining the incorporation of the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) with the immobilization of the antifungal Amphotericin B (AmB) on polydimethylsiloxane (PDMS) was developed in a two-step process. This novel strategy combines the key advantages of NO, a bactericidal agent and platelet inhibitor, with AmB, a potent antifungal agent. We demonstrated that SNAP-AmB surfaces significantly reduced the viability of adhered Staphylococcus aureus (99.0 ± 0.2%), Escherichia coli (89.7 ± 1.0%), and Candida albicans (93.5 ± 4.2%) compared to controls after 24 h of in vitro exposure. Moreover, SNAP-AmB surfaces reduced the number of platelets adhered by 74.6 ± 3.9% compared to controls after 2 h of in vitro porcine plasma exposure. Finally, a cytotoxicity assay validated that the materials did not present any cytotoxic side effects toward human fibroblast cells. This novel approach is the first to combine antifungal surface functionalization with NO-releasing technology, providing a promising step toward reducing the rate of broad-spectrum infection and thrombosis associated with indwelling medical devices.
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影响因子：
9.7
作者：
Brisbois EJ;Major TC;Goudie MJ;Bartlett RH;Meyerhoff ME;Handa H
通讯作者：
Handa H
影响因子：
39.2
作者：
Boogaerts, M;Winston, DJ;De Beule, K
通讯作者：
De Beule, K
影响因子：
3.9
作者：
Ghaffari, A;Miller, CC;Ghahary, A
通讯作者：
Ghahary, A
一氧化氮释放：第二部分。治疗应用。
影响因子：
46.2
作者：
Carpenter AW;Schoenfisch MH
通讯作者：
Schoenfisch MH
影响因子：
5.8
作者：
Colletta A;Wu J;Wo Y;Kappler M;Chen H;Xi C;Meyerhoff ME
通讯作者：
Meyerhoff ME