Effects of N-trimethyl chitosan chloride, a novel absorption enhancer, on Caco-2 intestinal epithelia and the ciliary beat frequency of chicken embryo trachea

N-trimethyl chitosan (TMC) polymers are quaternized chitosans in different degrees of trimethylation. These polymers enhance the absorption of macromo lecules through mucosal epithelia by triggering the reversible opening of t ight junctions and only allow for paracellular transport. To investigate th e safety of these novel absorption enhancers cytotoxicity and cilioloxicity studies have been performed. Intestinal Caco-2 cell monolayers were chosen to study possible membrane damaging effects of these polymers, using confo cal laser scanning microscopy visualization of nuclear staining by a membra ne impermeable fluorescent probe during transport of the paracellular marke r Texas red dextran (MW 10 000). Ciliated chicken embryo trachea tissue was used to study the effect of the polymers on the ciliary beat frequency (CB F) in vitro. In both studies the TMC polymers of different degrees of subst itution (20, 40 and 60%) were tested at a concentration of 1.0% (w/v). No s ubstantial cell membrane damage could be detected on the Caco-2 cells treat ed with TMCs, while the effect on the CBF in vitro was found to be marginal . TMC60 and TMC40 enhance paracellular transport of Texas red dextran in Ca co-2 cell monolayers, whereas TMC20 is ineffective. In conclusion, TMCs of high degrees of substitution may be effective and safe absorption enhancers for peptide and protein drug delivery. (C) 1999 Elsevier Science B.V. All rights reserved.