Preparation and evaluation of bovine serum albumin nanospheres coated with monoclonal antibodies.
Bovine serum albumin nanospheres (BSA-NS), prepared with glutaraldehyde cross-linking and ultrasonication, were coated with antibodies by covalent linkage (Schiff's base formation) of aldehyde groups at the surface of the nanospheres with amino groups of the antibody. The coating was confirmed using Fluorescein isothiocyanate which conjugates with antibodies and also by the antigen-antibody interaction using Sepharose beads. Rapid in vitro degradation of BSA-NS was first confirmed by incubating a radioactive nanosphere suspension at 37 degrees C in 0.25 M sucrose solution with 1% liver or lung extract. The radioactive compound conjugated BSA-NS suspension was then administered to mice intravenously, and tissue distribution of BSA-NS was examined using whole body autoradiography; the BSA-NS were found to be localized mainly in the liver, the lungs and the kidneys and 4 hr and 24 hr after injection, almost all radioactivity had disappeared except for that in the kidneys. The binding ratio of monoclonal antibodies to tumor cells in vitro was found to be 2-2.5 times greater than that of control antibodies (mouse IgG) by means of a gamma ray counter. An in vivo binding test showed that monoclonal antibodies might recognize the target organ (Lewis lung carcinoma). Applying these findings, BSA-NS coated with monoclonal antibodies were found to be trapped in the tumoral tissue of Lewis lung carcinoma-bearing mice more than in controls (BSA-NS coated with mouse IgG) at 24 hr after the injection. Thus, BSA-NS offer potential as useful drug carriers enabling concentration of drugs at specific target sites. Furthermore, their rapid elimination from the body and their degradability suggest that side effects due to long-lasting accumulation in several organs may be avoided.
Akasaka
Y
Y
Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Ueda
H
H
Takayama
K
K
Machida
Y
Y
Nagai
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis*; D001345:Autoradiography; D005260:Female; D007275:Injections, Intravenous; D007553:Isotope Labeling; D008631:Mercury Radioisotopes; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000032:analysis*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism; D014465:Ultrasonics
D000911:Antibodies, Monoclonal; D008631:Mercury Radioisotopes; D012710:Serum Albumin, Bovine