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用于HIV抗逆转录病毒疗法的口服每周一次给药系统的研发。

Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy.

作者信息

Kirtane Ameya R, Abouzid Omar, Minahan Daniel, Bensel Taylor, Hill Alison L, Selinger Christian, Bershteyn Anna, Craig Morgan, Mo Shirley S, Mazdiyasni Hormoz, Cleveland Cody, Rogner Jaimie, Lee Young-Ah Lucy, Booth Lucas, Javid Farhad, Wu Sarah J, Grant Tyler, Bellinger Andrew M, Nikolic Boris, Hayward Alison, Wood Lowell, Eckhoff Philip A, Nowak Martin A, Langer Robert, Traverso Giovanni

机构信息

Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Département Biosciences, Institut National des Sciences Appliquées de Lyon, 20 Avenue Albert Einstein, Villeurbanne, France, 69100.

出版信息

Nat Commun. 2018 Jan 9;9(1):2. doi: 10.1038/s41467-017-02294-6.

Abstract

The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.

摘要

药物治疗依从性不佳会显著降低抗逆转录病毒疗法的疗效。目前尚未开发出能够减轻每日服药负担的长效肠内给药系统。在此,我们描述了一种由不同药物 - 聚合物基质组成的口服剂型,该剂型在猪体内实现了抗逆转录病毒药物多替拉韦、利匹韦林和卡博特韦长达一周的全身药物水平。病毒动力学模拟和患者依从模式表明,此类系统将显著减少治疗失败,并且流行病学模型表明预防性使用这种干预措施可避免数十万新的艾滋病毒病例。总之,通过新型口服剂型每周给药长效抗逆转录病毒药物是一种有前景的干预措施,有助于在全球范围内控制艾滋病毒流行。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a2/5760734/d1d9d74a9f0a/41467_2017_2294_Fig1_HTML.jpg

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