Long-term vaginal antibody delivery: Delivery systems and biodistribution

• Published in: Biotechnology and bioengineering Vol. 67; no. 3; pp. 253 - 264
• Main Authors: Saltzman, W. Mark, Sherwood, Jill K., Adams, Dana R., Haller, Patricia
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 05.02.2000; Wiley
• Subjects: Administration, Intravaginal; Administration, Oral; Administration, Topical; Animals; Antibodies, Monoclonal - pharmacokinetics; Biological and medical sciences; Biomaterials; Blood; Body Fluids; controlled release; Delayed-Action Preparations; drug delivery; Drug Delivery Systems - methods; Drug dosage; Female; Humans; Immunization; Immunoglobulin G - pharmacology; Immunoglobulin M - pharmacology; Immunomodulators; Iodine Radioisotopes; Mathematical models; Medical sciences; Membranes, Artificial; Mice; Mice, Inbred C57BL; Monoclonal antibodies; Mucous Membrane; Pharmacokinetics; Pharmacology. Drug treatments; Physiological models; Plastic products; polymer; Polymers; Tissue; Tissue Distribution; Vagina; Vaginal Diseases - immunology; Vaginal Diseases - prevention & control; Delivery system; EVA; Intravaginal administration; Antibody; Controlled release form; Control release polymer
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/(SICI)1097-0290(20000205)67:3<253::AID-BIT1>3.0.CO;2-T

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 125I‐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 ∼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 ∼3 h; the half‐life for IgG1 clearance from the blood was >1 day; and the overall permeability constant for vaginal uptake of IgG was ∼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. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng 67: 253–264, 2000.