R. Nakaoka et al., ANTIBODY-PRODUCTION BY ADMINISTRATION OF BIODEGRADABLE GRANULES INCORPORATING ANTIGEN THROUGH DIFFERENT INJECTION ROUTES, Journal of controlled release, 40(1-2), 1996, pp. 11-21
Biodegradable poly(DL-lactic acid) granules containing ovalbumin (OVA)
, a model antigen, were administered by intraperitoneal, subcutaneous,
and intramuscular injection to mice to assess the effect of their inj
ection route on the production of OVA-specific antibody in serum. OVA
was released in vitro from the OVA-loaded granules over 35 days withou
t any initial burst. A single injection of the granules enhanced the s
erum level of anti-OVA IgG antibody at an early stage to a great exten
t compared with that of OVA injection in the water-soluble, free form,
although the titer level induced by their intraperitoneal injection w
as higher than that of other injection routes. The time course of anti
body production induced by the granules was independent of the injecti
on route and the enhanced antibody production lasted over a time perio
d of 22 weeks, which was much longer than that of free OVA injection.
A body distribution study demonstrated that the injection of OVA incor
porated into the granules reduced the serum concentration compared wit
h that of free OVA injection, irrespective of the injection route. It
is likely that the granules remained as a depot to gradually release O
VA around their injection site, leading to a high adjuvant effect for
the enhanced antibody production. In addition, a strong secondary resp
onse was observed for every mouse given the primary immunization of th
e OVA-loaded granules compared with that of free OVA injection, irresp
ective of their injection route. It was concluded that the granule is
a promising immunological adjuvant not only to enhance the antibody pr
oduction but also to prolong the production.