A comparative study of chitosan and chitosan/cyclodextrin nanoparticles as potential carriers for the oral delivery of small peptides.

The aim of this study was to characterize new nanoparticles (NPs) containing chitosan (CS), or CS/cyclodextrin (CDs), and evaluate their potential for the oral delivery of the peptide glutathione (GSH). More precisely, NP formulations composed of CS, CS/alpha-CD and CS/sulphobutyl ether-beta-cyclodextrin (SBE(7m)-beta-CD) were investigated for this application. CS/CD NPs showed particle sizes ranging from 200 to 500nm. GSH was loaded more efficiently in CS/SBE(7m)-beta-CD NPs by forming a complex between the tripeptide and the CD. X-ray Photoelectron Spectroscopy (XPS) analysis suggested that GSH is located in the core of CS/SBE(7m)-beta-CD NPs and that it is almost absent from the NP surface. Release studies performed in vitro at pH 1.2 and pH 6.8 showed that NP release properties can be modulated by selecting an appropriate CD. Transport studies performed in the frog intestine model confirmed that both CS and CS/CD nanoparticles could induce permeabilization of the intestinal epithelia. However, CS/SBE(7m)-beta-CD NPs provided absorption-enhancing properties in all segments of the duodenum, whereas CS NPs effect was restricted to the first segment of the duodenum. From the data obtained, we believe that CS/CD nanoparticles might represent an interesting technological platform for the oral administration of small peptides.