Long-term vaginal antibody delivery: Delivery systems and biodistribution

Topical delivery systems can provide prolonged delivery of antibodies to th e vaginal mucosal surface for long-term protection against infectious disea ses. We examined the biodistribution of antibodies during 30 days of vagina l antibody delivery in mice. Different antibody preparations (including mon oclonal IgG and IgM, as well as several different I-125-labeled IgGs) were administered by polymer vaginal rings, which were designed to provide conti nuous antibody delivery. Antibody concentrations remained high in the vagin al secretions for up to 30 days after disk insertion; radiolabeled antibody was also found, at similar to 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 sys temic concentrations as a function of antibody delivery and elimination rat es. Results from the model were consistent with previously reported antibod y pharmacokinetic measurements: the half-life for antibody elimination for the vagina was similar to 3 h; the half-life for IgG, clearance from the bl ood was >1 day; and the overall permeability constant for vaginal uptake of IgG was similar to 0.01 to 0.03 h(-1). These results provide important inf ormation for the design of controlled antibody delivery devices for vaginal use, and suggest that high-dose, longterm vaginal administration of antibo dies may be a reasonable approach for achieving sustained mucosal and syste mic antibody levels. (C) 2000 John Wiley & Sons, Inc.