Stability of antibody-bearing liposomes containing dideoxyinosine triphosphate

Abstract

Liposomes bearing surface-attached antibody were prepared to study the retention of dideoxyinosine triphosphate (ddITP). Liposomes of various lipid composition were prepared and conjugated with modified mouse monoclonal antibodies. The antibody (H-2-K k) used in this study is for Fc-mediated targeting. Antibody specificity was measured by studying the binding of antibody-liposome conjugates to antimouse IgG-Sepharose. The binding of antibody-liposome conjugates (L-Ab) was maximum when negatively charged liposomes (DMPC: CHOL: DCP) were employed. Inclusion of cholesterol to DMPC liposomes increased the binding by 4%. The binding was least when the neutral phospholipid compositions were employed (DMPC, DPPC and DMPC: CHOL) to prepare liposomes. The retention of ddITP was measured in plain liposomes and antibody-bearing liposomes stored at 4, 25 and 37°C. The leakage was maximal in DMPC liposomes. Only 20% of ddITP was retained in DMPC liposomes stored at 4°C after a month. However, when samples were stored at 25 and 37°C the retention was 12% and 4% respectively. There was no leakage of ddITP at 4 and 25°C in liposomes prepared using DMPC: CHOL (1:1 mole ratio) and DMPC: CHOL: DCP (7:2:1 mole ratio). The retention of ddITP was significantly increased in DMPC and DPPC liposomes after conjugation with antibodies. The retention of ddITP in DMPC: CHOL and DMPC: CHOL: DCP liposomes conjugated with antibodies was comparable to plain liposomes. These results suggest that the lipid composition used in the preparation of liposomes affect the conjugation of antibodies to liposomes and also the retention of an encapsulated drug.