Department of Medicine (Division of Dermatology), Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine, Bronx, NY, USA; Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara, SP, Brazil.
Nanomedicine. 2017 Oct;13(7):2267-2270. doi: 10.1016/j.nano.2017.06.018. Epub 2017 Jul 13.
Systemic therapies are preferred for treating dermal dermatophytosis due to inadequate penetration of topical agents. However, systemic antifungals are associated with off-target effects and limited tissue penetration, and antimicrobial resistance is a growing concern. To address this, we investigated topical nitric oxide-releasing nanoparticles (NO-np), which have been used against superficial fungal infections and bacterial abscesses. In addition to enhanced penetration and permeation conferred by nanoparticles, nitric oxide, a broad-spectrum multi-mechanistic antimicrobial agent, offers decreased likelihood of resistance development. In the current study, NO-np inhibited Trichophyton rubrum in vitro, as well as in a murine model of dermal dermatophytosis. In mice, NO-np reduced fungal burden after three days, with complete clearance after seven. Furthermore, NO-np decreased tissue IL-2, 6, 10 and TNFα, indicating earlier attenuation of the host inflammatory response and decreased tissue morbidity. Thus, topical NO-np represent an attractive alternative to systemic therapy against dermal T. rubrum infection.
系统治疗由于局部药物渗透不足，是治疗皮肤癣菌病的首选方法。然而，全身抗真菌药物与非靶向效应和有限的组织穿透有关，抗菌药物耐药性是一个日益严重的问题。为了解决这个问题，我们研究了局部释放一氧化氮的纳米粒子（NO-np），它已被用于治疗浅部真菌感染和细菌性脓肿。除了纳米粒子赋予的增强渗透和渗透作用外，一氧化氮作为一种广谱多机制的抗菌剂，降低了耐药性发展的可能性。在目前的研究中，NO-np 抑制了体外红色毛癣菌，以及皮肤癣菌病的小鼠模型。在小鼠中，NO-np 在三天后降低了真菌负荷，七天后完全清除。此外，NO-np 降低了组织中 IL-2、6、10 和 TNFα，表明宿主炎症反应更早减弱，组织发病率降低。因此，局部 NO-np 是治疗皮肤红色毛癣菌感染的全身治疗的一种有吸引力的替代方法。
