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一种可扩展的超长效应的特诺福维尔酸原药维持HBV抑制

Samiksha S Raut¹, Srijanee Das¹, Grace Bybee¹

¹Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Science advances

|August 1, 2025

概括

一种新的长效配方M5TFV在治疗艾滋病毒和乙型肝炎病毒 (HBV) 的同时感染方面表现有前途. 这种新型的tenofovir前药物有效地降低了小鼠的HBVDNA,支持其进一步发展.

科学领域:

药理学和病毒学
药物输送系统药物输送系统
乙型肝炎病毒 (HBV) 研究研究

背景情况:

长效 (LA) 配方在艾滋病毒治疗和预防方面取得了进展.
乙型肝炎病毒 (HBV) 与艾滋病毒的同时感染需要对两种病毒都有效的治疗方法.
现有的LA疗法缺乏针对HBV的活性.

研究的目的:

开发和评估一种新的,无氨基酸的,脂友的酸原药,用于特诺福维尔 (TFV) 的超长效应 (LA) 输送.
评估M5TFV纳米悬浮 (NM5TFV) 在治疗HBV感染中的安全性和有效性.

主要方法:

开发一种简化的,结晶的,没有氨基酸的TFV的酸原药 (M5TFV).
将M5TFV制成纳米悬浮剂 (NM5TFV),用于肌肉内注射.
将NM5TFV给Sprague-Dawley大鼠和HBV转基因小鼠,以评估耐受性和抗病毒活性.

主要成果:

在动物模型中,肌肉内注射NM5TFV的耐受性很好.
在HBV转基因小鼠中,单剂量NM5TFV在2个月以上的时间内证明了HBV DNA的持续减少 (>2.5 log10).
在肝细胞样细胞中观察到共闭圆形DNA (cccDNA) 的减少.

结论:

M5TFV是对抗HBV的超长效应配方的一个有希望的候选者.
这种新的前药物策略克服了与传统的ProTides相关的挑战.
NM5TFV需要进一步开发,以应对HIV/HBV共感染.

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