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

• Published in: European journal of pharmaceutics and biopharmaceutics 2010-05, Vol.75 (1), p.26-32
• Main Authors: Trapani, Adriana, Lopedota, Angela, Franco, Massimo, Cioffi, Nicola, Ieva, Eliana, Garcia-Fuentes, Marcos, Alonso, Maria José
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Chitosan; Cyclodextrins; Cyclodextrins - administration & dosage; Cyclodextrins - pharmacokinetics; Drug Carriers - administration & dosage; Drug Carriers - pharmacokinetics; Drug Delivery Systems - methods; General pharmacology; Glutathione; Glutathione - administration & dosage; Glutathione - pharmacokinetics; Intestinal Absorption - drug effects; Intestinal Absorption - physiology; Medical sciences; Nanoparticles; Nanoparticles - administration & dosage; Oral administration; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacokinetics; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rana esculenta
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2010.01.010

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/α-CD and CS/sulphobutyl ether-β-cyclodextrin (SBE 7m-β-CD) were investigated for this application. CS/CD NPs showed particle sizes ranging from 200 to 500 nm. GSH was loaded more efficiently in CS/SBE 7m-β-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-β-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-β-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.