Polyarginine Nanocapsules as a Potential Oral Peptide Delivery Carrier.

We have previously reported the development of novel nanocapsules made of polyarginine (PArg) specifically designed for the delivery of small anticancer drugs into cells. Our goal, in this work, has been to investigate the potential of these nanocarriers for oral delivery of peptide anticancer drugs. To reach this objective, we chose the antitumoral peptide, elisidepsin, and evaluated the characteristics of the PArg nanocapsules in terms of drug loading capacity, stability in simulated intestinal fluids, and ability to interact with the intestinal epithelium both in vitro (Caco-2 model cell line) and in vivo. Our results suggest that elisidepsin can be effectively loaded into the nanocapsules by adjusting the formulation parameters, using a solvent displacement technique. The resulting nanocapsules were stable upon incubation in simulated intestinal fluids and had the ability to reduce, in a transient manner, the transepithelial electrical resistance of the Caco-2 cell monolayer. Confocal images also revealed that PArg nanocapsules were internalized by the monolayer without evident signs of cytotoxicity. Finally, the in vivo fluorescent imaging study illustrates the retention of the nanocapsules in the gastrointestinal tract upon oral administration. Overall, the results underline the potential interest of PArg nanocapsules as carriers for the oral administration of peptide drugs.