Stearylamine Liposome as an Anti-Parasitic Agent

Janani Vassoudevane, Monika Mariebernard, V. Rajendran
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引用次数: 1

Abstract

The uncontrolled increasing clinical resistance to the current anti-parasitic drugs towards important protozoan parasites (Plasmodium, Leishmania, Trypanosoma and Toxoplasma) has stimulated the search for novel and safe therapeutic agents at affordable prices for countries in which these parasites are endemic. For the past few decades, the criticality of the cationic lipid stearylamine (SA) in liposomes has been explored in these human parasites. Previously, SA was incorporated in the liposomal formulation to impart a net positive charge for enhanced cellular uptake. However, the discovery of SA in liposomes alone elicits a strong anti-parasitic activity with immunomodulatory potential. Additionally, the SA liposome possesses a significant inhibitory potential on multiple life stages of the parasite cycle and delivers an equal effect on both drug-sensitive and resistant parasites. Moreover, the delivery of standard anti-parasitic drugs using SA liposome vesicles has enhanced the efficacy of drugs due to the synergistic impacts without causing any apparent toxicity on the host cells. In addition, the delivery of antigens as vaccine candidates using SA liposomes elicits a pronounced immune response in clearing the infection compared to other cationic lipids and SA-free liposomes. Nonetheless, SA liposome mediates its anti-parasitic activity by targeting the negatively charged phosphatidylserine-exposed infected host cell surface or by interaction with negatively charged sialic acid of free-living parasites. Overall, SA liposome confers its protection by acting as a chemotherapeutic agent with immunomodulatory activity. Therefore, a broadly acting anti-parasitic agent (SA liposome) is promising in tackling the deadly parasitic infections in endemic regions and warrants further clinical investigations.
硬脂胺脂质体的抗寄生虫作用
目前对重要原生动物寄生虫(疟原虫、利什曼原虫、锥虫病和弓形虫)的抗寄生虫药物的临床耐药性日益增加,这一不受控制的情况促使人们为这些寄生虫流行的国家寻找价格可承受的新型安全治疗药物。在过去的几十年里,人们一直在探索这些人类寄生虫脂质体中阳离子脂质硬脂胺(SA)的临界性。以前,SA被纳入到脂质体制剂中,以赋予净正电荷以增强细胞摄取。然而,在脂质体中发现SA具有很强的抗寄生虫活性,具有免疫调节潜力。此外,SA脂质体在寄生虫周期的多个生命阶段具有显著的抑制潜力,并且对药物敏感和耐药寄生虫具有相同的效果。此外,使用SA脂质体囊泡递送标准抗寄生虫药物由于协同作用而提高了药物的功效,而不会对宿主细胞产生任何明显的毒性。此外,与其他阳离子脂质和无SA脂质体相比,使用SA脂质体作为候选疫苗递送抗原可引起明显的免疫应答,以清除感染。尽管如此,SA脂质体通过靶向带负电荷的磷脂酰丝氨酸暴露的感染宿主细胞表面或通过与带负电荷的自由生活寄生虫唾液酸相互作用来介导其抗寄生虫活性。总的来说,SA脂质体通过作为一种具有免疫调节活性的化疗药物来赋予其保护作用。因此,一种广谱抗寄生虫剂(SA脂质体)有望解决流行地区的致命寄生虫感染,值得进一步的临床研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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