title: Absorption-promoting effects of chitosan in airway and intestinal cell lines: a comparative study.
abstract: This work explored the interaction of chitosan with Calu-3 and Caco-2 cell lines, as models of the airway and intestinal epithelium, respectively. The toxicity, tight junction opening and mucoadhesive effects of chitosan were compared in the two cell lines. Additionally, the role of mucus in the absorption-promoting activity of chitosan was studied systematically. Notably, chitosan exhibited a different degree of toxicity on the Calu-3 and Caco-2 cells. Chitosan's tight junction-opening effect, observed in terms of reduction of transepithelial electrical resistance and permeability enhancement, was apparent in both cell lines, though somewhat lower in Caco-2 compared to Calu-3 cell layers (though overall permeability was higher in the former). Tight junction opening and association of chitosan with the epithelial cell layers were more prominent in mucus-containing than in mucus-depleted Calu-3 cells and non mucus-excreting Caco-2 monolayers. Overall, the work suggests that chitosan exhibits a different level of toxicity in airway, as compared to intestinal cells and although absorption enhancement is apparent in both cell lines, enabling its potential use as an absorption-promoting excipient in both pulmonary and oral macromolecular delivery, the magnitude and the duration of the effect are dependent on the level of mucus present on the epithelial surfaces.
authors.affiliation: The School of Pharmacy, Boots Science Building, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom. Driton.Vllasaliu@nottingham.ac.uk
authors.forename: Driton
authors.initials: D
authors.lastname: Vllasaliu
authors.forename: Luca
authors.initials: L
authors.lastname: Casettari
authors.forename: Robyn
authors.initials: R
authors.lastname: Fowler
authors.forename: Ruth
authors.initials: R
authors.lastname: Exposito-Harris
authors.forename: Martin
authors.initials: M
authors.lastname: Garnett
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Illum
authors.forename: Snow
authors.initials: S
authors.lastname: Stolnik
mesh_terms: D000268:Adhesiveness; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D005079:Excipients / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D009093:Mucus / Q000378:metabolism; D010539:Permeability; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D005079:Excipients; D048271:Chitosan