关键词: Amphotericin B CNS infection Naegleria fowleri adverse effects blood–brain barrier brain-eating amoebae free-living amoebae intranasal route novel therapeutic delivery primary amoebic meningoencephalitis

Mesh : Amphotericin B Administration, Intranasal Blood-Brain Barrier Brain Liver

来  源:   DOI:10.4155/tde-2023-0032

Abstract:
Aim: CNS infections due to parasites often prove fatal. In part, this is due to inefficacy of drugs to cross the blood-brain barrier. Methods: Here, we tested intranasal and intravenous route and compared adverse effects of Amphotericin B administration, through blood biochemistry, liver, kidney and brain histopathological evidence of toxicities in vivo post-administration. Results: It was observed that intranasal route limits the adverse side effects of Amphotericin B, in contrast to intravenous route. Conclusion: As parasites such as Naegleria fowleri exhibit unequivocal affinity toward the olfactory bulb and frontal lobe in the central nervous system, intranasal administration would directly reach amoebae bypassing the blood-brain barrier selectivity and achieve the minimum inhibitory concentration at the target site.
Brain infections due to parasites are often fatal. One of the reasons is the inability of drugs to get to the brain. When given in large dose to reach the brain, the drug can cause serious side effects. Here, we tested the side effects of Amphotericin B (drug of choice against brain-eating amoebae), when given intranasally versus intravenous. Our findings clearly show that intranasal route limits the side effects of Amphotericin B. These are important findings and should serve as an important step in the development of effective therapy against parasitic infections affecting the brain.
摘要:
目的:由寄生虫引起的中枢神经系统感染通常是致命的。在某种程度上,这是由于药物穿过血脑屏障无效。方法:这里,我们测试了鼻内和静脉途径,并比较了两性霉素B给药的不良反应,通过血液生物化学,肝脏,给药后体内毒性的肾和脑组织病理学证据。结果:观察到鼻内途径限制了两性霉素B的不良副作用,与静脉途径相反。结论:由于寄生虫如鸡夜蛾对中枢神经系统的嗅球和额叶表现出明确的亲和力,鼻内给药将绕过血脑屏障选择性直接到达变形虫,并在目标部位达到最小抑制浓度。
寄生虫引起的脑部感染通常是致命的。原因之一是药物无法进入大脑。当大剂量给药到达大脑时,这种药物会引起严重的副作用。这里,我们测试了两性霉素B(针对吃脑变形虫的首选药物)的副作用,当给予鼻内与静脉注射。我们的发现清楚地表明,鼻内途径限制了两性霉素B的副作用。这些是重要的发现,应作为开发针对影响大脑的寄生虫感染的有效疗法的重要步骤。
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