Targetability of the pendant type polyethyleneglycol-immunoliposomes in vivo

Abstract

Drug delivery to specific cells by immunoliposomes represents a potentially attractive mode of therapy. However, though immunoliposomes are effective in specific binding to target cells in vitro, their targeting efficiency in vivo is relatively low. We have recently developed a new type of polyethyleneglycol (PEG)-immunoliposomes, so called a pendant type PEG-immunoliposome, which are carrying the monoclonal antibodies at the distal ends of PEG chains. Pendant type PEG-immunaliposomes showed high targetability in vivo. In this study, we have synthesized new other PEG derivatives with reactive residues at the distal terminal of PEG chains, i. e., DSPE-PEG-COOH, DPPE-PEG-Mal and DPPE-PEG-CDI. PEG-liposomes composed of ePC/CH (2:1, m/m) and 6 mol% of PEG derivative were prepared and a monoclonal IgG antibody, 34A, which is highly specific to pulmonary endothelial cells, was conjugated to the terminal of PEG-COOH-, PEG-Mal- or PEG-CDI-liposomes. PEG-liposomes without antibodies showed the prolonged circulation time and the reduced RES uptake. All 34A-PEG-immunoliposomes showed high targeting efficiency to the lung in BALB/c mice. This approach provides a simple means of conjugating antibodies or ligands directly, and should contribute to development of superior targetable drug delivery vesicles for use in diagnostics and therapy.