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Abstract

We have developed a new type of long-circulating immunoliposome (Fab'-PEG immunoliposomes) which is efficiently extravasated into the targeted solid tumor in vivo. Small unilamellar liposomes (100-130 nm in diameter) were prepared from distearoylphosphatidylcholine (DSPC), cholesterol (CHOL) and a dipalmitoylphosphatidylethanolamine derivative of PEG with a terminal maleimidyl group (DPPE-PEG-Mal), and conjugated Fab' fragment of antibody. Inclusion of DPPE-PEG-Mal and linkage of the Fab' fragment instead of intact antibody to PEG terminals allowed the liposomes to evade RES uptake and remain in the circulation for a long time, resulting in enhanced accumulation of the liposomes in the solid tumor. Because of the ability of such Fab'-PEG immunoliposomes to target solid tumors, they appear highly attractive as carriers of not only chemotherapeutic agents, but also of macromolecular drugs.

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PubMed ID:: 9287139

DOI:: 10.1016/S0014-5793(97)00905-8

ScienceOpen disciplines: Chemistry

Keywords: Animals,Carcinoembryonic Antigen,immunology,Cholesterol,chemistry,metabolism,Extravasation of Diagnostic and Therapeutic Materials,Female,Humans,Immunoglobulin Fab Fragments,therapeutic use,Liposomes,Liver,Maleimides,Mice,Mice, Inbred BALB C,Neoplasm Transplantation,Neoplasms, Experimental,Phosphatidylcholines,Phosphatidylethanolamines,Polyethylene Glycols,Stomach Neoplasms,therapy,Time Factors,Tumor Cells, Cultured

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ScienceOpen disciplines: Chemistry

Keywords: Animals, Carcinoembryonic Antigen, immunology, Cholesterol, chemistry, metabolism, Extravasation of Diagnostic and Therapeutic Materials, Female, Humans, Immunoglobulin Fab Fragments, therapeutic use, Liposomes, Liver, Maleimides, Mice, Mice, Inbred BALB C, Neoplasm Transplantation, Neoplasms, Experimental, Phosphatidylcholines, Phosphatidylethanolamines, Polyethylene Glycols, Stomach Neoplasms, therapy, Time Factors, Tumor Cells, Cultured

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