Controlled delivery of antibodies against leukocyte adhesion molecules from polymer matrices

[摘要] The interaction between infected leukocytes and mucosal epithelia is likely to play a critical role in the sexual transmission of certain diseases. It may be possible to prevent the transmission of intracellular pathogens by inhibiting leukocyte-epithelial interactions. Monoclonal antibodies (MAbs) against leukocyte adhesion receptors can provide specific and potent inhibition of leukocyte-epithelial interactions, but systemic delivery of such MAbs is not desirable; therefore, a new method for local delivery of anti-adhesion MAbs to an exposed mucosal surface was developed using polymeric controlled-release devices. To evaluate the prophylactic potential of MAbs, leukocyte adhesion to the apical surface of a monolayer of T84 cells was examined in the presence of MAbs against human leukocyte surface proteins. MAbs against the MAC-I adhesion receptor inhibited neutrophil attachment to T84 cells by as much as 97%. MAbs against murine leukocyte receptors were produced from several hybridomas and incorporated into poly(ethylene-co-vinyl acetate) (EVAc) devices. During incubation in buffered saline, small polymer discs continuously released active MAbs for 10 days. After insertion into the vaginal canals of mice, these polymer disks produced high levels of anti-MAC-1 MAb for several days. Polymeric controlled-release devices provide a new technique for using MAbs against adhesion receptors as a means of long-term, localized sexually transmitted disease (STD) prophylaxis.

[发布日期] 1996-12-01

[关键词] pharmacokinetics;monoclonal antibodies;integrins;leukocyte adhesion;T84 cells;poly(ethylene-co-vinyl acetate)