Immunoliposome

The "stealth" concept may offer two other opportunities for liposome application (1) Conventional immunoliposomes (see Sec. VI.C) have been shown to be removed rapidly firom the circulation by the MPS (Peeters et al., 1987). The combination of the stealth approach for longer circulation with the attachment of antibodies or antibody fragments may provide a means of delivery of drugs to their sites of action with a high degree of specificity. This could be useful for treating leukemia, graft-vs.-host diseases, and HIV disease. 

For a rational design of immunoliposomes a clear insight into the factors which control the disposition of liposomes in vivo is crucial (see Sec. V). In addition, there are other critical factors relevant to the use of immunoliposomes ... 

Recently we reviewed the literature (Peeters et al., 1987) dealing with the potential and limitations of immunoliposomes in the treatment... 

Peeters, P. A. M., Brunink, B. G., Eling, W. M. C., and Crommelin, D. J. A. (1989). Therapeutic effect of chloroquirie (CQ) containing immunoliposomes in rats infected with Plasmodium berghei parasitized mouse red blood cells comparison with combinations of antibodies and CQ or liposomal CQ, Biochim. Biophys Acta, 981, 269-276. 

Wang, C., and Huang, L. (1987). pH-sensitive immunoliposomes mediate target-cell-specific delivery and controlled expression of a foreign gene in mouse, Proc. Natl. Acad. Sci. USA, 84, 7851-7855. 

Figure 1. Schematic description of organ-specific immunoliposomes.

Tumor cells. EMT6 cells were grown as a monolayer culture in DMEM medium containing 20% fetal calf serum (27). Cells were detached from the plate by trypsin-EDTA treatment and washed in PBS. A total of 5 x 103 cells were injected per mouse via the tail vein of Balb/c mice (6-8 weeks old) to induce experimental lung metastatic tumors. Immunoliposomes were injected iv 2 and 4 days after the tumor cell injection. The survival of mice was followed over the next 60 days. 

Optimization of Immunoliposome Binding to the Lung. In order to reduce the uptake of immunoliposomes by the liver and spleen, we have tested the effect of incorporating GMj into the liposome membrane on the lung binding of immunoliposomes. We (74,22) and others (70,77,72) have demonstrated that the presence of this monosialoganglioside in the liposomes effectively reduces the RES uptake and prolongs the circulation time of liposomes. Since GMj contains one... 

Figure 3. Retention of immunoliposomes in lung. Immunoliposomes (200 /ig lipid) labeled with lxlIn-DTPA-SA were injected iv. The percent initial accumulation in lung was calculated at indicated time intervals. Bar is S.D. (n=3) Data taken with permission from reference 14. Key , 34A-liposomes (PC chol GMx=10 5 l), Ab lipid= 1 11 (w/w), 297 nm in average diameter A, 34A-liposomes (PC chol GM.=10 5 1), Ab lipid=l 37 (w/w), 292 nm in average diameter , 34A-liposomes (PC chol PS=10 5 1), Ab lipid=l 8 (w/w), 253 nm in average diameter A, 34A-liposomes (PC chol PS=10 5 1), Ab lipid=l 31 (w/w), 255 nm in average diameter.

Klibanov, A.L., Maruyama, K., Beckerleg, A.M., Torchilin, V.P., and Huang, L. (1991) Activity of amphip-athic polyethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding to target. Biochim. Biophys. Acta 1062, 142-148. 

Koning, G.A., Morselt, H.W., Velinova, M.J., Donga, J., Gorter, A., Allen, T.M., Zalipsky, S., Kamps, J.A., and Scherphof, G.L. (1999) Selective transfer of a lipophilic prodrug of 5-fluorodeoxyuridine from immunoliposomes to colon cancer cells. Biochim. Biophys. Acta 1420(1-2), 153-167. 

Huwyler J, Cerletti A, Fricker G, Eberle AN, Drewe J (2002) By-Passing of P-glycoprotein effect on digoxin uptake by immunoliposomes. J Drug Target 10 73-79... 

Huwyler J, Wu D, Pardridge WM (1996) Brain drug delivery of small molecules using immunoliposomes. Proc Natl Acad Sci USA 93 14164—14169... 

---