Sustained release of ATP encapsulated in chitosan oligosaccharide nanoparticles

The chemical cross-linked chitosan oligosaccharide (CSO) nanoparticles containing ATP/CSO ionic complex nano-components were prepared using combination techniques of W/O miniemulsion, chemical cross-linking and ionic complexation. The resulted nanoparticles had about 110 nm diameter and 20 mV surface zeta potential. The ATP loading efficiencies in nanoparticles could reach up to 40.6-69.5%. It was found that the ATP loading efficiency increased with increasing the amount and the molecular weight of chitosan oligosaccharide, and decreased with increasing molar ratio of glutaraldehyde to chitosan oligosaccharide. In vitro ATP release from chemical cross-linked CSO nanoparticles could continue for 24h, and could also be adjusted by the amount and molecular weight of CSO, and the molar ratio of glutaraldehyde to CSO. The higher molecular weight and smaller amount of CSO, and the lower molar ratio of glutaraldehyde to CSO led the slower ATP release rate. Furthermore, it was also found that the CSO nanoparticles could be uptaken by HepG-2 tumor cells, and could be applied for intracellular drug delivery.