Antibodies immunoliposomes

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. 

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. 

Figure 1.1. Schematic representation of four major liposome types. Conventional liposomes are either neutral or negatively charged. Stealth liposomes are sterically stabilized and carry a polymer coating to obtain a prolonged circulation time in the body. Immunoliposomes are antibody targeted liposomes and can consist of either conventional or sterically stabilized liposomes. Positive charge on cationic liposomes can be created in various ways. Reproduced from reference [112] with permission.

Figure 2.10. Schematic diagram of coupling of a thiolated antibody to a linker lipid (maleimide-PEG-phospholipid) which is part of a preformed liposome. The resulting thioether bond is meta-bolically stable. The strategy shown here was used to synthesize OX26-immunoliposomes [111].

Plasma clearance (Cl), blood-brain barrier permeability surface area product (PS) and accumulation as % injected dose detected in brain tissue (%ID tissue) at 1 h after administration. Results show free [ H]-daunomycin (Daunomycin), [ H]-daunomycin encapsulated in conventional liposomes (Liposomes), sterically stabilized liposomes (PEG-liposomes), immunoliposomes (29 0X26, where 29 designates the number of 0X26 mAb conjugated per liposome) and control immunoliposomes where the 0X26 mAb was replaced by a non-specific isotype control antibody (IgG2a). Values are means SEM of n = 3 experiments. 

Maruyama, K., T. Takizawa, T. Yuda, S.J. Kennel, L. Hnang, and M. Iwatsuru, Tar-getability of novel immunoliposomes modified with amphipathic poly(ethylene glycol)s conjugated at their distal terminals to monoclonal antibodies. Biochim Biophys Acta, 1995.1234(1) 74-80. 

Park, J. W., Kirpotin, D., Shalaby, R., Hong, K, Shao, Y., Marks, J., Papahadjopoulos, D., and Benz, C. C. (1998). Anti-HER2 immunoliposomes Significantly superior efficacy vs. doxorubicin, liposomal doxorubicin, and anti-her2 antibody treatment, via novel mechanism of action. Proc. Am. Soc. Clin. Oncol. 17, 216a. 

Immunoliposomes ( antibody-targeted ), which can be either conventional or sterically stabilized, are used for active-targeting purposes. 

Immunoliposomes have specific antibodies or antibody fragments on their surface to enhance target site binding. The primary focus of their use has been in the targeted delivery of anticancer agents. 

Long-circulating immunoliposomes can also be prepared (see Figure 5.8). The antibody can be coupled directly to the liposomal surface, however the PEG chains may provide steric hindrance to antigen binding. Alternatively, a bi-functional PEG linker can be used, to couple liposomes to one end of PEG chains and antibodies to the other end of these chains. Steric hindrance is not a problem in the latter approach. 

Liposomes can be targeted to the brain by exploiting receptor-mediated transcytosis systems. For example, a bi-functional PEG-linker has been used to couple anti-transferrin (0X26) receptor antibodies to one end of the PEG strands and liposomes at the other end of the PEG strands (Figure 13.6). Classically, immunoliposomes are prepared by attaching the MAb to the surface of the liposomes (see Section 5.3.1.3). However, this can lead to steric hindrance by the PEG strands with respect to antibody binding to the appropriate receptor. The use of the bifunctional PEG linker overcomes this problem. 

PEG-ylated immunoliposomes for CNS drug delivery. The drug is entrapped within a hposome vector to which is attached antibodies on poly(ethylene glycol) linkers... 

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