PMID: 3214439Nov 1, 1988Paper

Optimisation of the covalent binding of monoclonal antibodies to liposomes

Arzneimittel-Forschung
H P WeckenmannH Stricker

Abstract

Liposomes with covalently attached monoclonal antibody (mAb) may be useful for the active targeting of drugs, e.g. cytostatics, to tumor processes. For pharmacokinetic reasons the coupling reaction should be optimized with regard to the loading capacity, the number of IgG-molecules per liposome (N). The relative immunoreactivity of bound versus free mAb (r/r*) and the stability in biological fluids should be maximal, the particle size (phi) should be minimal. Furthermore, the coupling yield of the mAb should be high. This investigation was based on a previously described method, using N-hydroxysuccinimidyl-dithiopropionate for coupling anti-melanoma mAbs to liposomes composed of hydrogenated soybean lecithin, cholesterol and a dipalmitoyl-phosphatidylethanolamine derivative. Carboxyfluoresceine was used as a marker for the encapsulated phase. By systematic variation of 14 different reaction conditions a product with the following properties was obtained: N = 5, r/r* = 0.4 and phi = 120 nm. The average coupling yield was 39%. The specificity of liposomally bound mAb as assayed in in vitro tests was found to be unchanged.

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