Drug Delivery Using Antibody-Liposome Conjugates

Liposomes bearing surface-attached antibody (L-Ab) were prepared to deliver dideoxyinosine triphosphate (ddITP) to human monocyte/macrophages. A mouse monoclonal antibody (IgG2a) was modified using succinimidyl pyridyl dithiopropionate (SPDP) as a heterobifunctional reagent in order to conjugate the Ab to liposomes through a covalent (thioether) bond. SPDP-modified antibody was incubated with liposomes containing 5 mol% of maleimido phenyl butyrate phosphatidyl ethanolamine (MPB-PE) at room temperature for 8 hr. L-Ab was separated from free and aggregated antibodies by density gradient technique using metrizamide. Uptake of L-Ab by human monocyte/macrophages was measured as a function of time and compared to liposomes prepared with and without MPB-PE and free ddITP. The uptake increased with time with all samples except for free ddITP after 4 hr. This could be explained by dephosphorylation of ddITP. Uptake of MPB-PE liposomes was 2.7 times higher than those without MPB-PE after 48 hr. However, the uptake of L-Ab was 7 times higher than MPB-PE liposomes, 19 times higher than liposomes without MPB-PE, and 80 times higher than free ddITP after 48 hr. It can be concluded that the delivery of ddITP can be increased by surface attached antibody.