Barbour N P, Paborji M, Alexander T C, Coppola W P, Bogardus J B
Pharmaceutics Research and Development, Bristol-Myers Squibb Company, Syracuse, New York 13221, USA.
Pharm Res. 1995 Feb;12(2):215-22. doi: 10.1023/a:1016274825322.
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.
嵌合型BR96-阿霉素偶联物（BR96-DOX）是一种免疫偶联物，旨在特异性靶向并杀死某些肿瘤细胞。嵌合型BR96抗体与阿霉素之间的连接子是一个酸不稳定的腙基团，其设计目的是在体内经历溶酶体水解以释放阿霉素。稳定性研究表明，酸催化的腙水解是体外的主要降解途径。即使在最佳的pH和温度条件下，BR96-DOX在溶液中的稳定性对于长期储存来说也是不可接受的。在添加糖（如乳糖或蔗糖）的情况下对BR96-DOX进行冻干，并将冻干物随后冷藏保存，可显著提高其稳定性。因此，冻干似乎是实现BR96-DOX长期稳定的可行方法。
