Miconazole-splitomicin combined β-glucan hydrogel for effective prevention of Candida albicans periprosthetic joint infection

IF 4.3 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences Pub Date : 2024-11-04 DOI:10.1016/j.ejps.2024.106955

Menghan Wang , Ying Yang , Dongdong Li , Yanmei Wang , Tailin Ji , Qingqing Li , Jiye Zhang , Peipei Zhang , Jin Su

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引用次数: 0

Abstract

As one of the most common and serious infections caused by Candida albicans (C. albicans), periprosthetic joint infection (PJI) increasingly concerns surgeons and scientists. Generally, biofilms shield C. albicans from antifungal agents and immune clearance and induce drug-resistant strains. Developing novel strategies for PJI to get rid of current drug-resistant problems is highly needed. In our study, splitomicin (SP) can inhibit the mycelium formation of C. albicans and enhance the drug sensitivity of C. albicans to miconazole nitrate (MCZ). The combination of SP and MCZ significantly inhibited the viability, proliferation and adhesion of C. albicans, reduced the yeast to hyphae transition and biofilm formation. When SP and MCZ were coloaded in the β-glucan hydrogel, a viscoelastic solid with porous 3D network, sustained release and erosion properties was obtained. In the in vivo PJI mice model, SP-MCZ-β-glucan hydrogel effectively reduced the colonization and aggregation of C. albicans around the implant, reduced the pathological changes caused by C. albicans in the femur tissue. Therefore, SP-MCZ-β-glucan hydrogel holds a great promise for the management of C. albicans infection around joint prosthesis.

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咪康唑-斯利托米星联合β-葡聚糖水凝胶可有效预防白色念珠菌假体周围关节感染

作为由白色念珠菌（C. albicans）引起的最常见、最严重的感染之一，假体周围关节感染（PJI）越来越受到外科医生和科学家的关注。一般来说，生物膜会保护白念珠菌免受抗真菌药物和免疫清除的影响，并诱发耐药菌株。因此，亟需针对白僵菌感染开发新的策略，以解决目前的耐药问题。在我们的研究中，劈裂霉素（SP）能抑制白僵菌菌丝的形成，并增强白僵菌对硝酸咪康唑（MCZ）的药物敏感性。SP和硝酸咪康唑（MCZ）联用可明显抑制白僵菌的活力、增殖和粘附，减少酵母向菌丝的转化和生物膜的形成。在β-葡聚糖水凝胶中添加SP和MCZ后，可获得一种具有多孔三维网络、持续释放和侵蚀特性的粘弹性固体。在活体 PJI 小鼠模型中，SP-MCZ-β-葡聚糖水凝胶有效地减少了白僵菌在植入物周围的定植和聚集，减轻了白僵菌在股骨组织中引起的病理变化。因此，SP-MCZ-β-葡聚糖水凝胶在治疗关节假体周围白僵菌感染方面大有可为。

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来源期刊

European Journal of Pharmaceutical Sciences 医学-药学

CiteScore

9.60

自引率

2.20%

发文量

248

审稿时长

50 days

期刊介绍： The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.