title: Long-term vaginal antibody delivery: delivery systems and biodistribution.
abstract: Topical delivery systems can provide prolonged delivery of antibodies to the vaginal mucosal surface for long-term protection against infectious diseases. We examined the biodistribution of antibodies during 30 days of vaginal antibody delivery in mice. Different antibody preparations (including monoclonal IgG and IgM, as well as several different (125)I-labeled IgGs) were administered by polymer vaginal rings, which were designed to provide continuous antibody delivery. Antibody concentrations remained high in the vaginal secretions for up to 30 days after disk insertion; radiolabeled antibody was also found, at approximately 100 times lower concentration, in the blood and other tissues. The measured concentrations agreed reasonably well with a simple pharmacokinetic model, which was used to calculate mucosal and systemic concentrations as a function of antibody delivery and elimination rates. Results from the model were consistent with previously reported antibody pharmacokinetic measurements: the half-life for antibody elimination for the vagina was approximately 3 h; the half-life for IgG(1) clearance from the blood was >1 day; and the overall permeability constant for vaginal uptake of IgG was approximately 0.01 to 0.03 h(-1). These results provide important information for the design of controlled antibody delivery devices for vaginal use, and suggest that high-dose, long-term vaginal administration of antibodies may be a reasonable approach for achieving sustained mucosal and systemic antibody levels.
authors.affiliation: School of Chemical Engineering, Cornell University, Ithaca, New York 14853, USA. saltzman@cheme.cornell.edu
authors.forename: W M
authors.initials: WM
authors.lastname: Saltzman
authors.forename: J K
authors.initials: JK
authors.lastname: Sherwood
authors.forename: D R
authors.initials: DR
authors.lastname: Adams
authors.forename: P
authors.initials: P
authors.lastname: Castle
authors.forename: P
authors.initials: P
authors.lastname: Haller
mesh_terms: D000282:Administration, Intravaginal; D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D001826:Body Fluids; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007075:Immunoglobulin M / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008567:Membranes, Artificial; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane; D011108:Polymers; D014018:Tissue Distribution; D014621:Vagina; D014623:Vaginal Diseases / Q000276:immunology / Q000517:prevention & control
chemical_list: D000911:Antibodies, Monoclonal; D003692:Delayed-Action Preparations; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007457:Iodine Radioisotopes; D008567:Membranes, Artificial; D011108:Polymers