Design of an Antifungal Surface Embedding Liposomal Amphotericin B Through a Mussel Adhesive-Inspired Coating Strategy
Design of an Antifungal Surface Embedding Liposomal Amphotericin B Through a Mussel Adhesive-Inspired Coating Strategy
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DOI：
10.3389/fchem.2019.00431
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发表时间：
2019-06-18
影响因子：
5.5
通讯作者：
Pereira, Maria Olivia
中科院分区：
文献类型：
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作者：
Alves, Diana;Vaz, Ana Teresa;Pereira, Maria Olivia
导尿管的微生物定植仍然是医学上的一个严重问题，因为它经常导致生物膜形成和感染。在报道的处理这个问题的方法中，表面功能化使其具有抗菌特性，包括最有前途的一种。然而，这些策略中的大多数都是针对细菌生物膜而设计的，而真菌生物膜则少得多。在现实生活中，真菌将不可避免地与细菌一起被发现，特别是在生物材料领域。与抗菌方法相结合的抗真菌涂层策略的发展将是对抗生物材料相关感染的关键。因此，本研究的主要目标是设计一种有效的策略，用于将脂质体阿替霉素B（LAm B）固定在聚二甲基硅氧烷（PDMS）表面上，以防止白色念珠菌定植。使用两步贻贝启发的涂层策略进行固定，其中PDMS首先浸入多巴胺溶液中。它的聚合导致沉积一层薄的粘附膜，称为聚多巴胺（pDA），这使得LAmB的掺入，之后。筛选不同浓度的LAmB以获得不释放LAmB的接触杀伤表面。表面表征证实了多巴胺的聚合和进一步的功能化与LAmB产生的表面粗糙度更小，更亲水的功能。所提出的涂层策略使PDMS表面具有防止C附着的能力。白色念珠菌，并杀死粘附细胞，对哺乳动物细胞没有毒性。总体结果表明，LAmB固定在表面上保留其抗真菌活性和降低毒性，因此具有很大的潜力，可应用于导尿管的设计。由于通常发现的与这些装置相关的固着群落表现出多微生物的性质，下一个挑战将是将LAmB与抗菌剂共同作用，以防止导管相关性尿路感染（CANTI）的建立。
Microbial colonization of urinary catheters remains a serious problem for medicine as it often leads to biofilm formation and infection. Among the approaches reported to deal with this problem, surfaces functionalization to render them with antimicrobial characteristics, comprises the most promising one. Most of these strategies, however, are designed to target bacterial biofilms, while fungal biofilms are much less taken into account. In real-life settings, fungi will be inevitably found in consortium with bacteria, especially in the field of biomaterials. The development of antifungal coating strategies to be combined with antibacterial approaches will be pivotal for the fight of biomaterial-associated infections. The main goal of the present study was, therefore, to engineer an effective strategy for the immobilization of liposomal amphotericin B (LAmB) on polydimethylsiloxane (PDMS) surfaces to prevent Candida albicans colonization. Immobilization was performed using a two-step mussel-inspired coating strategy, in which PDMS is first immersed in dopamine solution. Its polymerization results in the deposition of a thin adherent film, called polydopamine (pDA), which allowed the incorporation of LAmB, afterwards. Different concentrations of LAmB were screened in order to obtain a contact-killing surface with no release of LAmB. Surface characterization confirmed the polymerization of dopamine and further functionalization with LAmB yielded surfaces with less roughness and more hydrophilic features. The proposed coating strategy rendered the surfaces of PDMS with the ability to prevent the attachment of C. albicans and kill the adherent cells, without toxicity toward mammalian cells. Overall results showed that LAmB immobilization on a surface retained its antifungal activity and reduced toxicity, holding therefore a great potential to be applied for the design of urinary catheters. Since the sessile communities commonly found associated to these devices exhibit a polymicrobial nature, the next challenge will be to co-immobilize LAmB with antibacterial agents to prevent the establishment of catheter-associated urinary tract infections (CAUTI).