title: Stabilization of chimeric BR96-doxorubicin immunoconjugate.
abstract: Chimeric BR96-doxorubicin conjugate (BR96-DOX) is an immunoconjugate designed to specifically target and kill certain tumor cells. The linker between the chimeric BR96 antibody and DOX is an acid-labile hydrazone group which was designed to undergo lysosomal hydrolysis to release DOX in vivo. Stability studies indicated that acid-catalyzed hydrazone hydrolysis was the major degradation route in vitro. Even under optimal conditions of pH and temperature, the stability of BR96-DOX in solution was not acceptable for long-term storage. Lyophilization of BR96-DOX in the presence of added sugars, such as lactose or sucrose, and subsequent storage of the lyophile under refrigeration significantly improved the stability. Therefore lyophilization appears to be a viable approach for achieving long-term stabilization of BR96-DOX.
authors.affiliation: Pharmaceutics Research and Development, Bristol-Myers Squibb Company, Syracuse, New York 13221, USA.
authors.forename: N P
authors.initials: NP
authors.lastname: Barbour
authors.forename: M
authors.initials: M
authors.lastname: Paborji
authors.forename: T C
authors.initials: TC
authors.lastname: Alexander
authors.forename: W P
authors.initials: WP
authors.lastname: Coppola
authors.forename: J B
authors.initials: JB
authors.lastname: Bogardus
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002021:Buffers; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D005612:Freeze Drying; D005615:Freezing; D006863:Hydrogen-Ion Concentration; D000922:Immunotoxins / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
chemical_list: D000911:Antibodies, Monoclonal; C092612:BR96-doxorubicin immunoconjugate; D002021:Buffers; D000922:Immunotoxins; D004317:Doxorubicin