Visualization of insulin-loaded nanocapsules: in vitro and in vivo studies after oral administration to rats.
OBJECTIVE
Biodegradable poly(isobutylcyanoacrylate) nanocapsules have been recognized as a promising carrier for oral administration of peptides and proteins. In the present study, we investigate the fate of insulin-loaded nanocapsules by fluorescence and transmission electron microscopy (TEM) after intragastric force-feeding to rats.


METHODS
Insulin-, Texas-red-labeled insulin, or gold-labeled insulin-loaded nanocapsules were first characterized. Rats received a single dose of nanocapsules (diameter 60-300 nm, 57 IU insulin/kg) by intragastric force-feeding. After 90 min, ileum was isolated and prepared for fluorescence and transmission electron microscopy.


RESULTS
Nanocapsules were observed on both sides of the gut epithelium and in blood capillaries. In M-cell-free epithelium, apparently intact nanocapsules could be seen in the underlying tissue, suggesting they could cross the epithelium and carry the encapsulated peptide. In M-cell-containing epithelium, nanocapsules appeared degraded in the vicinity of macrophages. It is noteworthy that intestinal absorption of nanocapsules was observed without artifacts forcing the nanocapsules to stay in the gut.


CONCLUSIONS
Based on TEM observations, this study shows the intestinal absorption of biodegradable nanocapsules leading to the transport of insulin across the epithelium mucosa. The fate of the nanocapsules appeared different depending on the presence or the absence of M cells in the intestinal epithelium.
Pinto-Alphandary
Huguette
H
UMR CNRS 8612, Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, Faculté de Pharmacie, Université Paris XI, 92296 Châtenay-Malabry Cédex, France. Huguette.Alphandary@cep.u-paud.fr
Aboubakar
Malam
M
Jaillard
Danielle
D
Couvreur
Patrick
P
Vauthier
Christine
C
D000284:Administration, Oral; D000818:Animals; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D036103:Nanotechnology / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin