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Long‐term vaginal antibody delivery: Delivery systems and biodistribution
Author(s) -
Saltzman W. Mark,
Sherwood Jill K.,
Adams Dana R.,
Haller Patricia
Publication year - 2000
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/(sici)1097-0290(20000205)67:3<253::aid-bit1>3.0.co;2-t
Subject(s) - antibody , biodistribution , pharmacokinetics , vagina , monoclonal antibody , drug delivery , chemistry , pharmacology , medicine , immunology , in vitro , surgery , biochemistry , organic chemistry
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 ∼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 IgG 1 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.