Tight junction modulation by chitosan nanoparticles: comparison with chitosan solution.
Present work investigates the potential of chitosan nanoparticles, formulated by the ionic gelation with tripolyphosphate (TPP), to open the cellular tight junctions and in doing so, improve the permeability of model macromolecules. A comparison is made with chitosan solution at equivalent concentrations. Initial work assessed cytotoxicity (through MTS and LDH assays) of chitosan nanoparticles and solutions on Calu-3 cells. Subsequently, a concentration of chitosan nanoparticles and solution exhibiting minimal toxicity was used to investigate the effect on TEER and macromolecular permeability across filter-cultured Calu-3 monolayer. Chitosan nanoparticles and solution were also tested for their effect on the distribution of the tight junction protein, zonnula occludens-1 (ZO-1). Chitosan nanoparticles produced a sharp and reversible decrease in TEER and increased the permeability of two FITC-dextrans (FDs), FD4 (MW 4 kDa) and FD10 (MW 10 kDa), with effects of a similar magnitude to chitosan solution. Chitosan nanoparticles produced changes in ZO-1 distribution similar to chitosan solution, indicating a tight junction effect. While there was no improvement in permeability with chitosan nanoparticles compared to solution, nanoparticles provide the potential for drug incorporation, and hence the possibility for providing controlled drug release and protection from enzymatic degradation.
Vllasaliu
Driton
D
The School of Pharmacy, Boots Science Building, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
Exposito-Harris
Ruth
R
Heras
Angeles
A
Casettari
Luca
L
Garnett
Martin
M
Illum
Lisbeth
L
Stolnik
Snow
S
D002460:Cell Line; D048271:Chitosan / Q000494:pharmacology*; D003911:Dextrans / Q000737:chemistry; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D053758:Nanoparticles; D010539:Permeability; D010750:Phosphoproteins / Q000378:metabolism; D012996:Solutions; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D003911:Dextrans; D008565:Membrane Proteins; D010750:Phosphoproteins; D012996:Solutions; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C015219:fluorescein isothiocyanate dextran; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate