Liposomes immunoliposomes

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. 

Nassander UK (1991) Liposomes, immunoliposomes, and ovarian carcinoma, PhD Thesis, Unviersity of Utrecht... 

Chemical composition Conventional liposomes (CL), pH sensitive liposomes, cationic liposomes, immunoliposomes and long circulating liposomes. The chemical composition of each liposome type gives particular characteristics to the final liposomal formulation that tnay be ideal for its systematic administration. 

Key words ATP, Liposomes, Immunoliposomes, Antimyosin, Ischemia, Isolated rat heart. Rabbit myocardial infarction... 

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 ... 

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. 

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. 

Figure 4 Cytotoxicity of HER2-directed liposomal APE in HER2-overexpressing BT474 human breast carcinoma cells. Cells were plated at a density of 5000 ceUs/well and incubated for four hours with varying concentrations of unencapsulated ( ), liposomal (O), or antiHER2 (E5)-immunoliposomal (A) Cells were assayed for viability using a standard tetrazolium-based assay three days later. Abbreviation. APE, 6-(3-aminopropyl)ellipticine.

Drummond DC, Marx C, Guo Z, et al. Enhanced pharmacodynamic and antitumor properties of a histone deacetylase inhibitor encapsulated in liposomes or ErbB2-targeted immunoliposomes. Clin Cancer Res 2005 11 3392-3401. Mamot C, Drummond Dc, Noble CO, et al. Epledermal growth factor receptor-targeted immunoliposomes significantly enhance the efficacy of multiple anticancer drugsin vivo. Cancer Res 2005 65 1631-1638. 

Carrion C, Domingo JC, de Madariaga MA. Preparation of long-circulating immunoliposomes using PEG-cholesterol conjugates effect of the spacer arm between PEG and cholesterol on liposomal characteristics. Chem Phys Lipids 2001 113 97. 

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].

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