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EnglishRed blood cells (RBC) may act as selective carriers of drugs to macrophages, an important reservoir of viruses such as human immunodeficiency virus (HIV) and herpes simplex virus type 1 (HSV-1). We therefore assessed the incorporation of 9-(2-phosphonylmethoxyethyl)adenine (PMEA, a potent inhibitor of HIV and HSV-1) into RBC, its delivery to macrophages and its activity against HIV or HSV-1. Loading of PMEA in artificially aged opsonized RBC affords significant levels of intracellular PMEA. RBC metabolize PMEA to its active congener PMEA-diphosphate, although with low efficiency. Exposure of macrophages to RBC-encapsulated PMEA inhibits the replication of both HIV and HSV-1 (about 90% inhibition at the highest RBC:macrophages ratios) even if RBC were removed before virus challenge. By contrast, the antiviral activity of free PMEA removed before virus challenge was irrelevant at concentrations up to 150-fold higher than the 50% effective concentration (EC50). Finally, the antiviral effect of RBC-encapsulated PMEA correlates with PMEA levels in macrophages about 500-fold higher than those achieved by free PMEA (at concentrations 10-fold higher than the EC50). The efficacy of RBC-mediated delivery to macrophages of PMEA (and perhaps of compounds with shorter intracellular half-lives) warrants further studies in infectious diseases involving phagocytizing cells as main targets of the pathogen.
Perno C.-F., S.N. (1997). Red blood cells mediated delivery of 9-(2-phosphonylmethoxyethyl)adenine to primary macrophages: Efficiency, metabolism and activity against human immunodeficiency virus or herpes simplex virus. ANTIVIRAL RESEARCH, 33(3), 153-164.
| Tipologia: | Articolo su rivista |
| Citazione: | Perno C.-F., S.N. (1997). Red blood cells mediated delivery of 9-(2-phosphonylmethoxyethyl)adenine to primary macrophages: Efficiency, metabolism and activity against human immunodeficiency virus or herpes simplex virus. ANTIVIRAL RESEARCH, 33(3), 153-164. |
| IF: | Con Impact Factor ISI |
| Lingua: | English |
| Settore Scientifico Disciplinare: | Settore MED/07 - Microbiologia e Microbiologia Clinica |
| Revisione (peer review): | Sì, ma tipo non specificato |
| Tipo: | Articolo |
| Rilevanza: | Rilevanza internazionale |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/S0166-3542(96)01011-X |
| Stato di pubblicazione: | Pubblicato |
| Data di pubblicazione: | 1997 |
| Titolo: | Red blood cells mediated delivery of 9-(2-phosphonylmethoxyethyl)adenine to primary macrophages: Efficiency, metabolism and activity against human immunodeficiency virus or herpes simplex virus |
| Autori: | |
| Autori: | Perno C.-F., Santoro N., Balestra E., Aquaro S., Cenci A., Lazzarino G., Pierro D.D., Tavazzi B., Balzarini J., Garaci E., Grimaldi S., Calio R. |
| Appare nelle tipologie: | 01 - Articolo su rivista |
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