Bezerra-Souza Adriana, Fernandez-Garcia Raquel, Rodrigues Gabriela F, Bolas-Fernandez Francisco, Dalastra Laurenti Marcia, Passero Luiz Felipe, Lalatsa Aikaterini, Serrano Dolores R
Laboratory of Pathology of Infectious Diseases (LIM-50), Medical School, University of São Paulo, Avenida Dr. Arnaldo 455, 01246903 Cerqueira César, SP, Brazil.
Departament of Pharmaceutics and Food Technology and Instituto Universitario de Farmacia Industrial (IUFI), School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, Spain.
Pharmaceutics. 2019 Jul 20;11(7):353. doi: 10.3390/pharmaceutics11070353.
Leishmaniasis is a neglected tropical disease affecting more than 12 million people worldwide, which in its visceral clinical form (VL) is characterised by the accumulation of parasites in the liver and spleen, and can lead to death if not treated. Available treatments are not well tolerated due to severe adverse effects, need for parenteral administration and patient hospitalisation, and long duration of expensive treatments. These treatment realities justify the search for new effective drugs, repurposing existing licensed drugs towards safer and non-invasive cost-effective medicines for VL. In this work, we provide proof of concept studies of butenafine and butenafine self-nanoemulsifying drug delivery systems (B-SNEDDS) against . Liquid B-SNEDDS were optimised using design of experiments, and then were spray-dried onto porous colloidal silica carriers to produce solid-B-SNEDDS with enhanced flow properties and drug stability. Optimal liquid B-SNEDDS consisted of Butenafine:Capryol 90:Peceol:Labrasol (3:49.5:24.2:23.3 /), which were then sprayed-dried with Aerosil 200 with a final 1:2 (Aerosil:liquid B-SNEDDS /) ratio. Spray-dried particles exhibited near-maximal drug loading, while maintaining excellent powder flow properties (angle of repose <10°) and sustained release in acidic gastrointestinal media. Solid-B-SNEDDS demonstrated greater selectivity index against promastigotes and -infected amastigotes than butenafine alone. Developed oral solid nanomedicines enable the non-invasive and safe administration of butenafine as a cost-effective and readily scalable repurposed medicine for VL.
利什曼病是一种被忽视的热带疾病，全球有超过1200万人受其影响。在内脏临床型（VL）中，其特征是寄生虫在肝脏和脾脏中积聚，若不治疗可导致死亡。由于严重的不良反应、需要肠胃外给药和患者住院治疗，以及昂贵治疗的持续时间长，现有的治疗方法耐受性不佳。这些治疗现状使得寻找新的有效药物成为必要，即将现有已获许可的药物重新开发为用于VL的更安全、非侵入性且具有成本效益的药物。在这项工作中，我们提供了布替萘芬及其自纳米乳化药物递送系统（B-SNEDDS）针对……的概念验证研究。使用实验设计对液体B-SNEDDS进行了优化，然后将其喷雾干燥到多孔胶体二氧化硅载体上，以制备具有增强流动性和药物稳定性的固体B-SNEDDS。最佳的液体B-SNEDDS由布替萘芬：辛酸癸酸甘油三酯90：聚乙二醇单油酸酯：Labrasol（3：49.5：24.2：23.3 /）组成，然后与气相二氧化硅2以最终1：2（气相二氧化硅：液体B-SNEDDS /）的比例进行喷雾干燥。喷雾干燥的颗粒表现出接近最大的药物负载量，同时保持优异的粉末流动性能（休止角<10°）并在酸性胃肠介质中持续释放。固体B-SNEDDS对前鞭毛体和感染的无鞭毛体表现出比单独使用布替萘芬更高的选择性指数。所开发的口服固体纳米药物能够以具有成本效益且易于扩大规模的方式将布替萘芬作为用于VL的非侵入性和安全药物进行给药。
