Inhibition of HIV-1 in Monocyte/Macrophage Cultures by 2′,3′-Dideoxycytidine-5′-Triphosphate, Free and in Liposomes*

Szebeni, János; Wahl, Sharon M.; Betageri, Guru V.; Wahl, Larry M.; Gartner, Suzanne; Popovič, Mikuláš; Parker, Robert; Black, Christopher D. V.; Weinstein, John N.

doi:10.1089/aid.1990.6.691

Cited by 42 publications

(12 citation statements)

References 30 publications

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“…In general, this physically controlled release method could be complementary to any other drug delivery and tagging mechanism, whether it is physical or chemical. Although AZTTP is used in the experiment, the ability of on-demand drug release by a MEN nano-carrier discovered in this study is also relevant to the treatment of other diseases such as many CNS diseases, cancer and others, where deep-tissue high-efficacy drug delivery at the sub-cellular level is key 12 .…”

Section: Discussionmentioning

confidence: 99%

“…For instance, as it is related to the delivery across the BBB, this approach provides a way to deliver drugs sufficiently fast to avoid their engulfing by the reticuloendothelial system. Nucleotide reverse transcriptase inhibitor 3 0 -azido-3 0 -deoxythymidine-5 0 -triphosphate (AZTTP) is among the most challenging anti-retroviral drugs to deliver across the BBB 12,13 . Previously we have shown that MNs tagged with AZTTP transmigrated across the BBB by the application of an external magnetic field without affecting the integrity of the BBB, and the transmigrated AZTTP demonstrated significant inhibition of HIV-1 p24 antigen production in an in vitro infection model system compared with the free AZTTP 14 .…”

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confidence: 99%

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Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers

et al. 2013

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Although highly active anti-retroviral therapy has resulted in remarkable decline in the morbidity and mortality in AIDS patients, inadequately low delivery of anti-retroviral drugs across the blood-brain barrier results in virus persistence. The capability of high-efficacytargeted drug delivery and on-demand release remains a formidable task. Here we report an in vitro study to demonstrate the on-demand release of azidothymidine 5 0 -triphosphate, an anti-human immunodeficiency virus drug, from 30 nm CoFe 2 O 4 @BaTiO 3 magneto-electric nanoparticles by applying a low alternating current magnetic field. Magneto-electric nanoparticles as field-controlled drug carriers offer a unique capability of field-triggered release after crossing the blood-brain barrier. Owing to the intrinsic magnetoelectricity, these nanoparticles can couple external magnetic fields with the electric forces in drug-carrier bonds to enable remotely controlled delivery without exploiting heat. Functional and structural integrity of the drug after the release was confirmed in in vitro experiments with human immunodeficiency virus-infected cells and through atomic force microscopy, spectrophotometry, Fourier transform infrared and mass spectrometry studies.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers

et al. 2013

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“…Broadly, there are four types of the liposomes mainly studied for the anti-HIV/AIDS drug delivery; these are cationic, anionic, sterically stabilized and immunoliposomes [18]. Encapsulated 2' ,3'-dideoxycytidine-5'-triphosphate in liposomes and compared its antiviral effect with the dideoxycytidine and dideoxycytidine-triphosphate in cultured human monocyte-macrophages infected with HIV-1 [93]. The antiviral effect and bone marrow toxicity of AZT-loaded liposomes in C57BL/6 mice Zidovudine was exploited by Phillips and co-workers [94].…”

Section: Dendrimersmentioning

confidence: 99%

“…Studies have been performed in order to overcome the phosphorylation step which is not feasible due to the presence of phosphatases which hydrolyse nucleotides into the corresponding nucleosides and to the poor permeability of cell membranes to the phosphatase form [114]. Thus, the phosphorylated form of zalcitabin was employed in order to overcome these limitations and to obtain site specific delivery [93]. This nanoformulation was investigated in humanmonocyte/macrophages infected with HIV-1.…”

Section: Dendrimersmentioning

confidence: 99%

Nanotechnology Approaches for Antiretroviral Drugs Delivery

Iannazzo¹,

Pistone²,

Romeo³

et al. 2015

Journal of AIDS and HIV infections

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The development of effective drug delivery approaches for the treatment of AIDS and HIV infection is a global challenge. The advent of multidrug, highly active antiretroviral therapy (HAART), have increased the life span of HIV-infected patients. However, it has not eradicated HIV infections, particularly in anatomically privileged sites, such as the brain, testes, gut, liver, kidney, and secondary lymphoid tissue. Several nanocarriers have been investigated in order to enhance the effective delivery of antiretroviral drugs for HIV prevention and therapy. This review focuses on the most recent and significant examples of nanotechnology-based approaches for the delivery of antiretroviral agents belonging to the classes of nucleoside-analog reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). Nanocarriers such as natural and synthetic polymeric nanoparticles, dendrimers, liposomes, and various drug conjugates have been discussed. These nanotechnology carriers are able to deliver the antiretroviral agents in a controlled and/or targeted manner thereby increasing the drug bioavailability and residence time at target sites with a considerable improvement in quality of HIV patients.

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“…Incubation was terminated by washing the suspended or adhered cells three times in ice-cold phosphate-buffered saline and lysing them with trichloroacetic acid. Details of the extraction process and analysis of the neutralized acid extract by high-pressure liquid chromatography (HPLC) are described elsewhere (1,13). Control experiments with [3H]AZT triphosphate (20 Ci/mmol; Moravek) revealed that the AZT phosphates remained unchanged during the preparative procedures described above.…”

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confidence: 99%

Effects of thymidine and uridine on the phosphorylation of 3'-azido-3'-deoxythymidine (zidovudine) in human mononuclear cells

Szebeni

Patel

Hung

et al. 1991

Antimicrob Agents Chemother

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The effects of thymidine and uridine on the phosphorylation of 3'-azido-3'-deoxythymidine (AZT) were studied in various human mononuclear cell preparations. Thymidine suppressed [3H]AZT phosphorylation in the same concentration range (20 to 100 ,uM) in which it antagonizes the anti-human immunodeficiency virus activity of AZT. Uridine, in turn, had no influence on AZT phosphorylation, just as it has no effect on the anti-human immunodeficiency virus activity of AZT. These findings are consistent with a close relationship between the inhibition of AZT phosphorylation and the influence of physiological nucleosides on the antiviral activity of AZT.The antiviral activities of 3'-azido-3'-deoxythymidine (AZT; zidovudine) and other 2',3'-dideoxynucleoside drugs in human immunodeficiency virus (HIV)-infected cells is thought to depend on three main factors: (i) the efficiency of phosphorylation to the triphosphate form, (ii) the efficiency with which the triphosphates inhibit viral reverse transcriptase, and (iii) the influence of physiological nucleosides on the former two processes (8). Concerning the last effect, it has been shown in ATH8 cells (9) and peripheral blood mononuclear cells (PBMC) (11) that thymidine (dThd) counteracts the antiviral activity of AZT. Uridine (Urd), on the other hand, was found not to affect the antiviral activity of AZT, although it antagonized the cytotoxic effect of AZT on bone marrow progenitor cells in a granulocyte-macrophage CFU assay (11). On this basis, Urd was suggested to have potential use in the treatment of human immunodeficiency virus (HIV) infections as a rescue from the hematologic side effects of AZT (11).To help understand the molecular basis of the abovedescribed phenomena, we asked in the present study whether the different effects of dThd and Urd on the anti-HIV action of AZT in PBMC and on the cytotoxicity of AZT in bone marrow mononuclear cells (BMMC) could be correlated with the effects of these nucleosides on the phosphorylation of AZT in these cells.Since monocytes constitute 20 to 30% of PBMC and since nucleoside metabolism is thought to differ between lymphoid cells and monocyte-macrophage lineage cells, purified monocytes and monocyte-derived macrophages (M/M) were subjected to separate analyses as well.PBMC were prepared from blood freshly drawn from healthy volunteers, and BMMC were prepared from a bone marrow aspirate from a healthy donor by Ficoll-Paque gradient centrifugation (5). Washed mononuclear cells were suspended in Dulbecco's modified Eagle's medium supplemented with L-glutamine, 10% heat-inactivated fetal calf serum, 4.5 g of D-glucose per liter, and antibiotics (D-MEM). Monocytes were separated from PBMC by counterflow centrifugal elutriation (16,17) and suspended in D-MEM (-3 x 107/ml). To prepare M/M, we plated monocytes in six-well * Corresponding author.Costar plates (5 x 106 cells per well) and cultured them for 1 day before starting the experiment.[3H]AZT (20 Ci/mmol) was from Moravek Biochemicals (Brea, Calif.). To measure AZT phosphoryl...

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Inhibition of HIV-1 in Monocyte/Macrophage Cultures by 2′,3′-Dideoxycytidine-5′-Triphosphate, Free and in Liposomes*

Cited by 42 publications

References 30 publications

Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers

Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers

Nanotechnology Approaches for Antiretroviral Drugs Delivery

Effects of thymidine and uridine on the phosphorylation of 3'-azido-3'-deoxythymidine (zidovudine) in human mononuclear cells

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