Inhibition of HIV-1 replication in macrophages by red blood cell-mediated delivery of a heterodinucleotide of lamivudine and tenofovir.
Homo- and heterodimers of nucleoside/nucleotide analogues as reverse transcriptase inhibitors are effective on HIV-1-infected human monocyte-derived macrophages (M/M) compared to the single drugs or their combination. Since the combined treatment of lamivudine (3TC) and tenofovir ((R)PMPA) has an antiretroviral efficacy and a synergic effect respect to separate drugs, the heterodinucleotide 3TCpPMPA was synthesized. A single administration of the dimer as free drug or 3TCpPMPA-loaded RBC selectively targeted to M/M was able to almost completely protect macrophages from "de novo" infection.
Franchetti
P
P
Department of Chemical Sciences, University of Camerino, Camerino, Italy.
Cappellacci
L
L
Petrelli
R
R
Vita
P
P
Grifantini
M
M
Rossi
L
L
Pierigé
F
F
Serafini
S
S
Magnani
M
M
Balestra
E
E
Perno
C-F
CF
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D016503:Drug Delivery Systems; D015195:Drug Design; D004912:Erythrocytes / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D019259:Lamivudine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D063065:Organophosphonates / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D000068698:Tenofovir; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D063065:Organophosphonates; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine