Chemical Engineering Department, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad, Iran.
Cutaneous Leishmaniasis Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Am J Trop Med Hyg. 2023 Jun 12;109(2):301-314. doi: 10.4269/ajtmh.23-0116. Print 2023 Aug 2.
Leishmaniasis is a parasitic disease caused by Leishmania parasites. Meglumine antimoniate, or Glucantime, is the primary drug used to treat this disease. Glucantime with a standard painful injection administration route has high aqueous solubility, burst release, a significant tendency to cross into aqueous medium, rapid clearance from the body, and insufficient residence time at the injury site. Topical delivery of Glucantime can be a favorable option in the treatment of localized cutaneous leishmaniasis. In this study, a suitable transdermal formulation in the form of nanostructured lipid carrier (NLC)-based hydrogel containing Glucantime was prepared. In vitro drug release studies confirmed controllable drug release behavior for hydrogel formulation. An in vivo permeation study on healthy BALB/C female mice confirmed appropriate penetration of hydrogel into the skin and sufficient residence time in the skin. In vivo performance of the new topical formulation on the BALB/C female mice showed a significant improvement in reduction of leishmaniasis wound size, lowering parasites number in lesions, liver, and spleen compared with commercial ampule. Hematological analysis showed a significant reduction of the drug's side effects, including variance of enzymes and blood factors. NLC-based hydrogel formulation is proposed as a new topical administration to replace the commercial ampule.
利什曼病是一种由利什曼原虫引起的寄生虫病。葡甲胺锑酸钠,或葡聚糖,是治疗这种疾病的主要药物。具有标准疼痛注射给药途径的葡聚糖具有高水溶性、爆发释放、向水性介质显著穿透的趋势、从体内快速清除以及在损伤部位的停留时间不足。葡聚糖的局部给药可能是治疗局部皮肤利什曼病的一种有利选择。在这项研究中,制备了一种合适的基于纳米结构脂质载体(NLC)的水凝胶形式的透皮制剂,其中包含葡聚糖。体外药物释放研究证实了水凝胶制剂具有可控的药物释放行为。在健康 BALB/C 雌性小鼠上进行的体内渗透研究证实了水凝胶适当渗透到皮肤中,并在皮肤中有足够的停留时间。新的局部制剂在 BALB/C 雌性小鼠上的体内性能显示,与商业安瓿相比,减少利什曼病伤口面积、降低病变、肝脏和脾脏中的寄生虫数量有显著改善。血液分析表明,药物的副作用,包括酶和血液因素的变化,显著减少。提出基于 NLC 的水凝胶制剂作为替代商业安瓿的新的局部给药方式。