Moosavian Seyedeh Alia, Fallah Maryam, Jaafari Mahmoud Reza
Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, 91775-1365, Iran.
Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Exp Parasitol. 2019 May;200:30-35. doi: 10.1016/j.exppara.2019.03.004. Epub 2019 Mar 18.
Topical treatment of cutaneous leishmaniasis has demonstrated appropriate alternative for reducing toxicity of conventional treatments, improving patients' compliance and reducing treatment costs. Furthermore, outbreak of cutaneous leishmaniasis in war and conflict zones emerges finding an effective, economical and user-friendly treatment. In the context of liposomal topical drug delivery, we developed and characterized meglumine antimoniate (MA) loaded liposomes and investigated their effectiveness in topical treatment of cutaneous leishmaniasis. Previously, we showed the promising use of liposomal formulation of MA in treatment of cutaneous leishmaniasis in BALB/c mice. Here, we included Stearylamine (SA) in liposomes' structure which has antileishmanial activity by itself. . Size and encapsulation efficiency of liposomes were measured and in vitro permeation was performed using mice model. In vitro toxicity of liposomes was measured against leishmania promastigotes and amastigotes. Liposomes were used topically twice a day for 4 weeks to treat leishmania lesions in BALB\c mice model. In vitro permeation study showed liposomal formulations improved the percent of MA permeation compared with MA-cream. Promastigotes and amastigotes assay results showed significant enhanced toxicity in Liposomal-MA containing SA compared to Lip-MA. In BALB\c mice model of cutaneous leishmaniasis, liposomal groups exhibited significantly smaller lesion size compared to control groups (p < 0.01). In addition, the spleen parasite burden was significantly (P < 0.01) lower in mice treated with selected liposomal MA than in mice treated with PBS, control liposomes and MA cream. The results of this study showed that SA-liposomes encapsulated with MA might be useful as a candidate for the topical treatment of CL which merit further investigation.
皮肤利什曼病的局部治疗已被证明是一种合适的替代方法，可降低传统治疗的毒性，提高患者的依从性并降低治疗成本。此外，在战争和冲突地区爆发的皮肤利什曼病需要找到一种有效、经济且用户友好的治疗方法。在脂质体局部给药的背景下，我们开发并表征了载有葡甲胺锑酸盐（MA）的脂质体，并研究了它们在皮肤利什曼病局部治疗中的有效性。此前，我们已表明MA脂质体制剂在治疗BALB/c小鼠皮肤利什曼病方面具有良好前景。在此，我们在脂质体结构中加入了本身具有抗利什曼活性的硬脂胺（SA）。测量了脂质体的大小和包封效率，并使用小鼠模型进行了体外渗透实验。测定了脂质体对利什曼原虫前鞭毛体和无鞭毛体的体外毒性。脂质体每天局部使用两次，持续4周，以治疗BALB/c小鼠模型中的利什曼病损伤。体外渗透研究表明，与MA乳膏相比，脂质体制剂提高了MA的渗透百分比。前鞭毛体和无鞭毛体检测结果显示，与Lip-MA相比，含SA的脂质体-MA的毒性显著增强。在皮肤利什曼病的BALB/c小鼠模型中，脂质体组的损伤大小明显小于对照组（p<0.01）。此外，与用PBS、对照脂质体和MA乳膏治疗的小鼠相比，用选定的脂质体MA治疗的小鼠的脾脏寄生虫负荷显著降低（P<0.01）。本研究结果表明，包封有MA的SA脂质体可能作为皮肤利什曼病局部治疗的候选药物，值得进一步研究。
