STUDIES ON POLYPEPTIDE DRUG DELIVERY SYSTEMS - TISSUE DISTRIBUTION OF IMMUNOGLOBULIN-G CONJUGATED WITH LECITHIN

As a study of drug delivery system for bioactive polypeptides, human immunoglobulin G (IgG), selected as a model peptide, was lecithinized and its distribution into various organs in mice and the affinity of the peptide to lymphocytes and cancer cells was evaluated. Amino lecithin, synthesized by introducing an amino group into the side chain of lecithin at position 2, was bound to IgG using carbodiimide. Assay of protein and phosphorus showed that about 60 lecithin molecules were covalently bound to one IgG molecule. Lecithinized IgG labeled with I-125 was intravenously injected into C3H/HeN mice and distribution into various organs was determined. The lecithinized IgG produced very high concentrations in the liver, kidneys and spleen. The lecithinized IgG showed a high affinity to human lymphocytes, and MM46 and sarcoma 180 cancer cells in vitro. A thyroid stimulating hormone receptor antibody was lecithinized by the same method. The antibody retained the activity after lecithinization. Thus, lecithinized polypeptides produced by covalently binding lecithin to peptides showed characteristics similar to those of lipid microsphere (LM) that we had developed for a drug delivery system for lipophilic drugs, in terms of the tissue distribution, and lecithinization is expected to be an effective approach to the development of drug delivery system for bioactive polypeptides.