Journal of Antimicrobial Chemotherapy, Vol 39, 63-69, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
IS Barsoum, KM Kopydlowski, P Cuenin and JA Setterstrom
The purpose of this study was to determine if the sustained release of
ampicillin from a biodegradable drug-delivery system (microencapsulated
ampicillin anhydrate (MEAA)) will increase or decrease the intensity of a
hypersensitivity reaction compared with that observed with free drug.
Ovalbumin, which is known to elicit a marked hypersensitivity reaction in
guinea pigs, and microencapsulated ovalbumin (MOVA) were tested in parallel
with ampicillin and MEAA. Guinea pigs were sensitized biweekly by
subcutaneous and intramuscular injections of ampicillin, MEAA, ovalbumin,
MOVA or placebo microspheres (test articles), each mixed with Freund's
adjuvant, and challenged 2 weeks later, intradermally, with the free
compounds. In a separate set of experiments, guinea pigs were sensitized by
implantation of the same agents in the caudal thigh of anaesthetized
animals. Skin allergic reactions were tested at 1 and 3 weeks following
local implantation of the test articles. Sera of sensitized guinea pigs
were tested for specific IgG antibodies by enzyme-linked immunosorbent
assay, and skin samples from the site of the inflammatory reaction were
fixed, stained and evaluated histologically. Guinea pigs sensitized
systemically with MEAA or MOVA showed smaller, but not statistically
different skin allergic response than animals given corresponding free
compounds. However, guinea pigs sensitized by local implantation of MEAA
showed a significantly lower inflammatory response (P < 0.0001) than
those given an equivalent dose of the free drug. Guinea pigs sensitized
with placebo microspheres showed a low inflammatory skin reaction which was
similar to those sensitized with all doses of MEAA. There was no
significant difference in specific IgG antibody response in the sera of
guinea pigs sensitized locally with either free or microencapsulated
ampicillin or ovalbumin. Histology of skin revealed a milder inflammatory
reaction with MEAA or MOVA than with ampicillin or ovalbumin, respectively.
We conclude that the encapsulated ampicillin or ovalbumin and subsequent
release of each agent will elicit a reduced hypersensitivity reaction in
guinea pigs than will the free agent.
JOURNAL ARTICLE
Evaluation of hypersensitivity to microencapsulated ampicillin in guinea pigs
US Army Dental Research Detachment, Walter Reed Army Institute of Research, Washington, DC 20307-5300, USA.
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