de Carvalho Patricio Beatriz Ferreira, da Silva Lopes Pereira Juliana Oliveira, Sarcinelli Michelle Alvares, de Moraes Bianca Portugal Tavares, Rocha Helvécio Vinicius Antunes, Gonçalves-de-Albuquerque Cassiano Felippe
Pharmacology Laboratory, Biomedical Institute, Federal University of State of Rio de Janeiro, 94 Frei Caneca Street, Rio de Janeiro 20211-010, Brazil.
Postgraduate Program in Molecular and Cell Biology, Biomedical Institute, Federal University of State of Rio de Janeiro, 94 Frei Caneca Street, Rio de Janeiro 20211-010, Brazil.
Pharmaceutics. 2022 Dec 3;14(12):2707. doi: 10.3390/pharmaceutics14122707.
Fungal diseases are a significant cause of morbidity and mortality worldwide, primarily affecting immunocompromised patients. , , and are opportunistic fungi and may cause severe lung disease. They can develop mechanisms to evade the host immune system and colonize or cause lung disease. Current fungal infection treatments constitute a few classes of antifungal drugs with significant fungi resistance development. Amphotericin B (AmB) has a broad-spectrum antifungal effect with a low incidence of resistance. However, AmB is a highly lipophilic antifungal with low solubility and permeability and is unstable in light, heat, and oxygen. Due to the difficulty of achieving adequate concentrations of AmB in the lung by intravenous administration and seeking to minimize adverse effects, nebulized AmB has been used. The pulmonary pathway has advantages such as its rapid onset of action, low metabolic activity at the site of action, ability to avoid first-pass hepatic metabolism, lower risk of adverse effects, and thin thickness of the alveolar epithelium. This paper presented different strategies for pulmonary AmB delivery, detailing the potential of nanoformulation and hoping to foster research in the field. Our finds indicate that despite an optimistic scenario for the pulmonary formulation of AmB based on the encouraging results discussed here, there is still no product registration on the FDA nor any clinical trial undergoing ClinicalTrial.gov.
真菌病是全球发病和死亡的重要原因，主要影响免疫功能低下的患者。曲霉属、念珠菌属和隐球菌属是机会性真菌，可能导致严重的肺部疾病。它们可以形成逃避宿主免疫系统的机制，并在肺部定植或引发疾病。目前的真菌感染治疗方法包括几类抗真菌药物，但真菌耐药性发展显著。两性霉素B（AmB）具有广谱抗真菌作用，耐药发生率低。然而，AmB是一种高度亲脂性的抗真菌药物，溶解度和渗透性低，在光、热和氧气中不稳定。由于静脉给药难以在肺部达到足够浓度的AmB，并试图将不良反应降至最低，因此已使用雾化两性霉素B。肺部给药途径具有起效迅速、作用部位代谢活性低、能够避免首过肝代谢、不良反应风险较低以及肺泡上皮厚度薄等优点。本文介绍了肺部递送两性霉素B的不同策略，详细阐述了纳米制剂的潜力，并希望推动该领域的研究。我们的研究结果表明，尽管基于本文讨论的令人鼓舞的结果，两性霉素B肺部制剂前景乐观，但美国食品药品监督管理局（FDA）仍未批准任何产品注册，ClinicalTrial.gov上也没有正在进行的临床试验。
