DNA-loaded chitosan oligosaccharide nanoparticles with enhanced permeability across Calu-3 cells

Yiqing Ye, Yingying Xu, Wanling Liang, George P.H. Leung, King Ho Cheung, Caihong Zheng, Fengying Chen, Jenny K.W. Lam*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

19 Citations (Scopus)


Chitosan oligosaccharide (oligoCS) is a low molecular weight chitosan and its potential for DNA delivery is described here. DNA-loaded oligoCS nanoparticles were prepared by ionic gelation using thiamine pyrophosphate (TPP) as cross-linker. The nanoparticles with oligoCS:DNA: TPP weight ratio of 50:1:25 were approximately 170nm in diameter with a zeta potential of +40mV, and were used in the permeability study. The cytotoxicity of oligoCS solutions and nanoparticles was evaluated by MTT assay. The concentrations that exhibited minimal cytotoxicity were employed to investigate their effect on trans-epithelial electrical resistance (TEER) and cellular uptake across the Calu-3 cell layer which was used as a nasal epithelial model. OligoCS nanoparticles were able to cause a significant and reversible decrease in TEER and promote efficient cellular uptake. In addition, the oligoCS nanoparticles were able to enhance paracellular permeability to a greater extent than oligoCS solutions at an equivalent concentration. However, the oligoCS nanoparticles were too large to cross the cell layers through the paracellular route. The transcellular pathway appeared to be the major mechanism of the transportation of oligoCS nanoparticles across the cell layers. OligoCS nanoparticles also allowed efficient DNA incorporation, thereby providing the possibility of controlled nucleic acids release and absorption across epithelial surface.

Original languageEnglish
Pages (from-to)474-486
Number of pages13
JournalJournal of Drug Targeting
Issue number5
Publication statusPublished - May 2013

Scopus Subject Areas

  • Pharmaceutical Science

User-Defined Keywords

  • Chitosan
  • Drug delivery
  • Gene delivery vehicles
  • Nanoparticles
  • Paracellular
  • Transcellular


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