Insulin-loaded nanocapsules for oral administration: In vitro and in vivo investigation

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.