Chitosan-glutathione conjugate-coated poly(butyl cyanoacrylate) nanoparticles: Promising carriers for oral thymopentin delivery

Thymopentin (TP5)-loaded poly(butyl cyanoacrylate) nanoparticles (TP5-PBCA-NPs) were prepared and their efficacies for oral delivery were evaluated before and after coating with chitosan or chitosan-glutathione conjugate (chitosan-GSH).TP5-PBCA-NPs were prepared by using optimized emulsion polymerization. Chitosan-GSH or chitosan was coated onto the surface of TP5-PBCA-NPs utilizing electrostatic interactions. Particle size, zeta potential, entrapment efficiency. TP5 bioactivity and in vitro drug release behavior, were examined. The pharmacodynamical studies on oral administration of these nanoparticles were performed using FACScan flow cytometry. All the drug-loaded nanoparticles increased the CD3(+), CD4(+) and CD8(+) T lymphocytes counts of the immune dysfunction rats compared with the TP5 solution but only chitosan-GSH-coated TP5-PBCA-NPs restored the T lymphocytes level to normal (p < 0.05). These results suggest that the hydrophobic PBCA-NPs could be used to improve the oral bioavailability of hydrophilic peptides. Chitosan and chitosan-GSH coated nanoparticles probably enhanced the efficacy, because of increased mucoadhesive capacity. This was particularly the case for the chitosan-GSH coated nanoparticles. (C) 2011 Elsevier Ltd. All rights reserved.