Long-Acting, Potent Delivery of Combination Antiretroviral Therapy

Anna H.F. Andersen; Camilla F. Riber; Kaja Zuwala; Martin Tolstrup; Frederik Dagnæs-Hansen; Paul W. Denton; Alexander N. Zelikin

doi:10.1021/acsmacrolett.8b00179

Long-Acting, Potent Delivery of Combination Antiretroviral Therapy

Anna H.F. Andersen, Camilla F. Riber, Kaja Zuwala, Martin Tolstrup, Frederik Dagnæs-Hansen, Paul W. Denton, Alexander N. Zelikin

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Antiretroviral therapy (ART) has revolutionized HIV treatment, yet grand challenges remain: (i) short blood and body residence time of the antiviral drugs, (ii) relative poor antiretroviral drug penetrance into key tissue reservoirs of viral infection, namely, the spleen and lymph nodes, and (iii) obstacles in different pharmacokinetics of the necessary combination drugs. We present a novel drug delivery approach that simultaneously overcomes these limitations. We designed albumin-polymer-drug conjugates where albumin ensures long body residence time as well as lymphatic accumulation of the conjugate. The polymer enabled the delivery of combinations of drugs in precise ratios affording potency superior to the individual antiretroviral drugs and strong protection from HIV infection in primary human T cells.

Original language	English (US)
Pages (from-to)	587-591
Number of pages	5
Journal	ACS Macro Letters
Volume	7
Issue number	5
DOIs	https://doi.org/10.1021/acsmacrolett.8b00179
State	Published - May 15 2018
Externally published	Yes

ASJC Scopus subject areas

Organic Chemistry
Polymers and Plastics
Inorganic Chemistry
Materials Chemistry

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10.1021/acsmacrolett.8b00179

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title = "Long-Acting, Potent Delivery of Combination Antiretroviral Therapy",

abstract = "Antiretroviral therapy (ART) has revolutionized HIV treatment, yet grand challenges remain: (i) short blood and body residence time of the antiviral drugs, (ii) relative poor antiretroviral drug penetrance into key tissue reservoirs of viral infection, namely, the spleen and lymph nodes, and (iii) obstacles in different pharmacokinetics of the necessary combination drugs. We present a novel drug delivery approach that simultaneously overcomes these limitations. We designed albumin-polymer-drug conjugates where albumin ensures long body residence time as well as lymphatic accumulation of the conjugate. The polymer enabled the delivery of combinations of drugs in precise ratios affording potency superior to the individual antiretroviral drugs and strong protection from HIV infection in primary human T cells.",

author = "Andersen, {Anna H.F.} and Riber, {Camilla F.} and Kaja Zuwala and Martin Tolstrup and Frederik Dagn{\ae}s-Hansen and Denton, {Paul W.} and Zelikin, {Alexander N.}",

note = "Funding Information: The authors wish to thank Kaja Borup L{\o}vschall for assistance with SEC analyses. We wish to acknowledge financial support from the Danish Council for Independent Research, Technology and Production Sciences, Denmark (ANZ; project DFF − 4184-00177) and from amfAR, The Foundation for AIDS Research (grant No 109328-59-RGRL). Publisher Copyright: Copyright {\textcopyright} 2018 American Chemical Society.",

year = "2018",

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doi = "10.1021/acsmacrolett.8b00179",

language = "English (US)",

volume = "7",

pages = "587--591",

journal = "ACS Macro Letters",

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T1 - Long-Acting, Potent Delivery of Combination Antiretroviral Therapy

AU - Andersen, Anna H.F.

AU - Riber, Camilla F.

AU - Zuwala, Kaja

AU - Tolstrup, Martin

AU - Dagnæs-Hansen, Frederik

AU - Denton, Paul W.

AU - Zelikin, Alexander N.

N1 - Funding Information: The authors wish to thank Kaja Borup Løvschall for assistance with SEC analyses. We wish to acknowledge financial support from the Danish Council for Independent Research, Technology and Production Sciences, Denmark (ANZ; project DFF − 4184-00177) and from amfAR, The Foundation for AIDS Research (grant No 109328-59-RGRL). Publisher Copyright: Copyright © 2018 American Chemical Society.

PY - 2018/5/15

Y1 - 2018/5/15

N2 - Antiretroviral therapy (ART) has revolutionized HIV treatment, yet grand challenges remain: (i) short blood and body residence time of the antiviral drugs, (ii) relative poor antiretroviral drug penetrance into key tissue reservoirs of viral infection, namely, the spleen and lymph nodes, and (iii) obstacles in different pharmacokinetics of the necessary combination drugs. We present a novel drug delivery approach that simultaneously overcomes these limitations. We designed albumin-polymer-drug conjugates where albumin ensures long body residence time as well as lymphatic accumulation of the conjugate. The polymer enabled the delivery of combinations of drugs in precise ratios affording potency superior to the individual antiretroviral drugs and strong protection from HIV infection in primary human T cells.

AB - Antiretroviral therapy (ART) has revolutionized HIV treatment, yet grand challenges remain: (i) short blood and body residence time of the antiviral drugs, (ii) relative poor antiretroviral drug penetrance into key tissue reservoirs of viral infection, namely, the spleen and lymph nodes, and (iii) obstacles in different pharmacokinetics of the necessary combination drugs. We present a novel drug delivery approach that simultaneously overcomes these limitations. We designed albumin-polymer-drug conjugates where albumin ensures long body residence time as well as lymphatic accumulation of the conjugate. The polymer enabled the delivery of combinations of drugs in precise ratios affording potency superior to the individual antiretroviral drugs and strong protection from HIV infection in primary human T cells.

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ER -

Long-Acting, Potent Delivery of Combination Antiretroviral Therapy

Abstract

ASJC Scopus subject areas

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