The purpose of this work was to investigate the ability of poly(isobutylcya
noacrylate) nanocapsules to protect insulin from degradation by proteolytic
enzymes providing biologically active insulin by the oral route. Insulin w
as labeled with Texas Red(R) for release studies and microscopy observation
s. The fluorescent marker was mostly retained by the nanocapsules incubated
in the reconstituted gastric medium but the release was 75% within 30 min
when the nanocapsules were incubated in the reconstituted intestinal medium
. Turbidimetric measurements and electron microscopy observations confirmed
that the nanocapsules were degraded in the reconstituted intestinal medium
, whereas nanocapsule integrity was preserved in the reconstituted gastric
medium. In vivo studies of the gastrointestinal distribution of insulin-loa
ded nanocapsules after oral feeding showed that nanocapsules were retained
by the stomach for 30 min. One hour after oral administration, nanocapsules
reached the lower part of the intestine (ileum). Fluorescence microscopy a
nd confocal microscopy carried out on portions of the small intestine revea
led the presence of concentrated fluorescent spots into the mucosa and even
in the lamina propia, suggesting that insulin-loaded nanocapsules could cr
oss the intestinal epithelium. These data suggest that PIBCA nanocapsules c
an efficiently protect insulin when given orally. In addition, they seemed
to be significantly involved in the absorption mechanism. Drug Dev. Res. 49
:109-117, 2000. (C) 2000 Wiley-Liss, Inc.