Inhibition of HIV-1 in monocyte/macrophage cultures by 2',3'-dideoxycytidine-5'-triphosphate, free and in liposomes

J. Szebeni; S. M. Wahl; G. V. Betageri; L. M. Wahl; S. Gartner; M. Popovic; R. J. Parker; C. D V Black; J. N. Weinstein

Inhibition of HIV-1 in monocyte/macrophage cultures by 2',3'-dideoxycytidine-5'-triphosphate, free and in liposomes

J. Szebeni, S. M. Wahl, G. V. Betageri, L. M. Wahl, S. Gartner, M. Popovic, R. J. Parker, C. D V Black, J. N. Weinstein

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

Abstract

The antiviral effects of 2',3'-dideoxycytidine (ddC), 2,3'-dideoxycytidine-5'-triphosphate (ddCTP) and liposome-encapsulated ddCTP [L(ddCTP)] were compared in cultured human monocyte-macrophages (M/M) infected with HIV-1. These treatments inhibited virus replication at nanomolar drug levels with activities in the order ddC > ddCTP = L(ddCTP). Studies on drug stability and uptake suggest that a large part of the free ddCTP is dephosphorylated before entering the cells, whereas L(ddCTP) remains stable over days and is taken up, probably by endocytosis. The response to L(ddCTP) suggests that the capability of liposomes for targeting drugs to macrophages in vivo could potentially be exploited to improve the therapeutic index of dideoxynucleoside drugs.

Original language	English (US)
Pages (from-to)	691-702
Number of pages	12
Journal	AIDS Research and Human Retroviruses
Volume	6
Issue number	5
State	Published - 1990
Externally published	Yes

ASJC Scopus subject areas

Immunology
Virology

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@article{a56038ba5a2e455093a2ece3277d44f3,

title = "Inhibition of HIV-1 in monocyte/macrophage cultures by 2',3'-dideoxycytidine-5'-triphosphate, free and in liposomes",

abstract = "The antiviral effects of 2',3'-dideoxycytidine (ddC), 2,3'-dideoxycytidine-5'-triphosphate (ddCTP) and liposome-encapsulated ddCTP [L(ddCTP)] were compared in cultured human monocyte-macrophages (M/M) infected with HIV-1. These treatments inhibited virus replication at nanomolar drug levels with activities in the order ddC > ddCTP = L(ddCTP). Studies on drug stability and uptake suggest that a large part of the free ddCTP is dephosphorylated before entering the cells, whereas L(ddCTP) remains stable over days and is taken up, probably by endocytosis. The response to L(ddCTP) suggests that the capability of liposomes for targeting drugs to macrophages in vivo could potentially be exploited to improve the therapeutic index of dideoxynucleoside drugs.",

author = "J. Szebeni and Wahl, {S. M.} and Betageri, {G. V.} and Wahl, {L. M.} and S. Gartner and M. Popovic and Parker, {R. J.} and Black, {C. D V} and Weinstein, {J. N.}",

year = "1990",

language = "English (US)",

volume = "6",

pages = "691--702",

journal = "AIDS Research and Human Retroviruses",

issn = "0889-2229",

publisher = "Mary Ann Liebert Inc.",

number = "5",

}

TY - JOUR

T1 - Inhibition of HIV-1 in monocyte/macrophage cultures by 2',3'-dideoxycytidine-5'-triphosphate, free and in liposomes

AU - Szebeni, J.

AU - Wahl, S. M.

AU - Betageri, G. V.

AU - Wahl, L. M.

AU - Gartner, S.

AU - Popovic, M.

AU - Parker, R. J.

AU - Black, C. D V

AU - Weinstein, J. N.

PY - 1990

Y1 - 1990

N2 - The antiviral effects of 2',3'-dideoxycytidine (ddC), 2,3'-dideoxycytidine-5'-triphosphate (ddCTP) and liposome-encapsulated ddCTP [L(ddCTP)] were compared in cultured human monocyte-macrophages (M/M) infected with HIV-1. These treatments inhibited virus replication at nanomolar drug levels with activities in the order ddC > ddCTP = L(ddCTP). Studies on drug stability and uptake suggest that a large part of the free ddCTP is dephosphorylated before entering the cells, whereas L(ddCTP) remains stable over days and is taken up, probably by endocytosis. The response to L(ddCTP) suggests that the capability of liposomes for targeting drugs to macrophages in vivo could potentially be exploited to improve the therapeutic index of dideoxynucleoside drugs.

AB - The antiviral effects of 2',3'-dideoxycytidine (ddC), 2,3'-dideoxycytidine-5'-triphosphate (ddCTP) and liposome-encapsulated ddCTP [L(ddCTP)] were compared in cultured human monocyte-macrophages (M/M) infected with HIV-1. These treatments inhibited virus replication at nanomolar drug levels with activities in the order ddC > ddCTP = L(ddCTP). Studies on drug stability and uptake suggest that a large part of the free ddCTP is dephosphorylated before entering the cells, whereas L(ddCTP) remains stable over days and is taken up, probably by endocytosis. The response to L(ddCTP) suggests that the capability of liposomes for targeting drugs to macrophages in vivo could potentially be exploited to improve the therapeutic index of dideoxynucleoside drugs.

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M3 - Article

C2 - 2163269

AN - SCOPUS:0025081562

SN - 0889-2229

VL - 6

SP - 691

EP - 702

JO - AIDS Research and Human Retroviruses

JF - AIDS Research and Human Retroviruses

IS - 5

ER -

Inhibition of HIV-1 in monocyte/macrophage cultures by 2',3'-dideoxycytidine-5'-triphosphate, free and in liposomes

Abstract

ASJC Scopus subject areas

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