Preparation and biological evaluation of polymerizable antibody Fab' fragment targeted polymeric drug delivery system.
A new polymerizable antibody Fab' fragment with a PEG spacer (MA-PEG-Fab') was prepared from OV-TL 16 antibody, specific against the OA-3 antigen expressed on most human ovarian carcinomas. The MA-PEG-Fab' possessed a higher reactivity in the copolymerization with N-(2-hydroxypropyl)methacrylamide (HPMA) than the polymerizable Fab' fragment MA-Fab' with a short spacer. The MA-PEG-Fab' was copolymerized with HPMA and MA-Gly-Phe-Leu-Gly-Mce(6) producing an Fab' targeted HPMA copolymer-Mce(6) conjugate. The number and weight average molecular weights of the copolymer were 164000 and 271000 Da, respectively. About two MA-PEG-Fab' fragments per chain were incorporated in the copolymer conjugates. Preliminary in vivo antitumor studies indicated that the Fab' targeted conjugates showed a higher efficacy of tumor growth inhibition in nude mice than the non-targeted conjugate.
Lu
Z R
ZR
Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, 30 S 2000 E Rm 301, University of Utah, Salt Lake City, UT 84112, USA.
Shiah
J G
JG
Kopecková
P
P
Kopecek
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems; D005079:Excipients; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D007167:Immunotherapy; D008689:Methacrylates; D051379:Mice; D008970:Molecular Weight; D010051:Ovarian Neoplasms / Q000628:therapy; D011092:Polyethylene Glycols; D011108:Polymers; D013056:Spectrophotometry, Ultraviolet
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D005079:Excipients; D007140:Immunoglobulin Fab Fragments; D008689:Methacrylates; D011108:Polymers; D011092:Polyethylene Glycols; C032802:hydroxypropyl methacrylate