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Liposomes bearing surface-attached antibody (L-Ab) molecules can be used for various purposes including the immunospecific delivery of drugs or other materials to antigenic target cells. In this study, L-Ab were prepared to deliver an anti-human immunodeficiency virus (HIV) drug, dideoxycytidine triphosphate (ddCTP) to human monocyte/macrophages. Cells of the monocyte/macrophage lineage are an important reservoir of HIV-1. A mouse monoclonal antibody IgG2a was labelled with 125I and modified using N succinimidyl-3-(2-pyridyldithio)propionate (SPDP) as a heterobifunctional reagent in order to conjugate with liposomes to produce a covalent bond (thioether). SPDP-modified antibody was incubated with liposomes containing 5 mol% of maleimido phenyl butyrate phosphatidylethanolamine (MPB-PE) at room temperature (21 degrees C) for 24 h. L-Ab were separated from free and aggregated antibodies by centrifugation. L-Ab were characterized by measuring particle size and binding to anti-mouse IgG-sepharose. Ninety five per cent of the liposomal (L-Ab) lipid label was bound to anti-mouse IgG-sepharose, whereas only 7% of plain liposomes were bound, indicating non-specific binding. Uptake of L-Ab was measured in human monocyte/macrophages as a function of time and compared with that of plain liposomes. The uptake increased with time and it was 4-6 times greater than that of plain liposomes although part of that effect may have been due to unreacted MPB groups.

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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 greater than 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.