A murine model of cutaneous aspergillosis for evaluation of biomaterials-based local delivery therapies.
A murine model of cutaneous aspergillosis for evaluation of biomaterials-based local delivery therapies.
复制标题
用于评估基于生物材料的局部递送疗法的皮肤曲霉病小鼠模型。
DOI：
10.1002/jbm.a.36671
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Mikos,AntoniosG
中科院分区：
文献类型：
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作者：
Tatara,AlexanderM;Watson,Emma;Albert,NathanielD;Kontoyiannis,PanayiotisD;Kontoyiannis,DimitriosP;Mikos,AntoniosG
皮肤真菌感染是一种具有挑战性的疾病，主要困扰着免疫功能低下的患者。局部抗真菌治疗可能允许将高浓度的抗真菌药物直接输送到伤口，同时将全身毒性降至最低。然而，该领域目前缺乏适合活体模型的。因此，在免疫抑制的小鼠身上造成较大的皮肤创伤，并接种烟曲霉菌。我们制备了可生物降解的聚合物微粒(MPS)，能够局部传递抗真菌药物，并对其体外释放动力学进行了表征。我们比较了用抗真菌MPS治疗的小鼠的伤口床大小、真菌负荷和真菌的组织学存在情况。以皮肤缺损但未感染的小鼠、皮肤缺损感染但未治疗的小鼠和空白MPS处理的感染小鼠为对照。大伤口的感染抑制愈合，并以接种依赖的方式导致组织侵袭。MPS能释放A以上浓度的抗真菌药物。熏蒸最低抑菌浓度(MIC)至少6天。经MPS处理的创面明显缩小(64.2%比19.4%，p=0.002)，与未感染对照组(64.2%比58.1%，p=0.497)无显著差异。这种小鼠模型可能有助于更好地了解皮肤真菌感染和评估基于局部生物材料的治疗。2019 Wiley期刊，Inc.生物材料资源A部分：107A：1867-1874,2019年。
Cutaneous fungal infection is a challenging condition to treat that primarily afflicts immunocompromised patients. Local antifungal therapy may permit the delivery of high concentrations of antifungals directly to wounds while minimizing systemic toxicities. However, the field currently lacks suitablein vivomodels. Therefore, a large cutaneous wound was created in immunosuppressed mice and inoculated withAspergillus fumigatus. We fabricated biodegradable polymer microparticles (MPs) that were capable of locally delivering antifungal and characterizedin vitrorelease kinetics. We compared wound bed size, fungal burden, and histological presence of fungi in mice treated with antifungal‐loaded MPs. Mice with a cutaneous defect but no infection, mice with infected cutaneous defect but no treatment, and infected mice treated with blank MPs were used as controls. Infection of large wounds inhibited healing and resulted in tissue invasion in an inoculum‐dependent manner. MPs were capable of releasing antifungals at concentrations aboveA. fumigatusMinimum Inhibitory Concentration (MIC) for at least 6 days. Wounds treated with MPs had significantly decreased size compared with no treatment (64.2% vs. 19.4% wound reduction,p= 0.002) and were not significantly different from uninfected controls (64.2% vs. 58.1%,p= 0.497). This murine model may serve to better understand cutaneous fungal infection and evaluate local biomaterials‐based therapies. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1867–1874, 2019.