Purpose: We have previously shown that high molecular weight (MW > 100 kDa) chitosan nanocapsules are efficient vehicles for improving the oral absorption of salmon calcitonin (sCT). In the present work, our objectives were, first, to investigate the influence of some formulation parameters on the efficacy of chitosan nanocapsules as carriers for the oral administration of sCT and, second, to elucidate the mechanism of interaction of chitosan nanocapsules with intestinal model cell lines.
Methods: sCT-loaded chitosan nanocapsules were prepared by the solvent displacement technique. They were characterized for their size, zeta potential, and sCT loading. The ability of chitosan nanocapsules to enhance the oral absorption of sCT was investigated in rats by monitoring the serum calcium levels. Finally, the mechanism of interaction of chitosan nanocapsules with the Caco-2 cell model or in the coculture of Caco-2 with HT29-M6 cells was investigated by confocal fluorescence microscopy.
Results: Chitosan nanocapsules presented a particle size in nanometer range, a positive surface charge, and an efficient encapsulation of sCT. Following oral administration to rats, all formulations of nanocapsules exhibited the ability to reduce calcemia levels; however, the intensity of the response varied depending on the formulation conditions. With regard to the mechanism of interaction of chitosan nanocapsules with cell culture, the xz images evidenced that chitosan nanocapsules interact and remain associated to the apical side of both model cell cultures. In addition, chitosan nanocapsules showed a preferable association to the mucus-secreting cells (HT29-M6).
Conclusions: Chitosan nanocapsules are able to enhance and prolong the intestinal absorption of sCT and this effect could be mainly ascribed to their mucoadhesive character and intimate interaction with the intestinal barrier.