A novel mucosal absorption enhancer: 2-guanidyl chitosan

Abstract

Guanidyl chitosan derivatives were synthesized with aminoiminomethanesulfonic acid. The architecture of guanidino function in the final product was confirmed by elemental analysis, 13C-NMR spectrum and Sakaguchi color test. Five guanidyl chitosan derivatives with Mw ranging from 16.2 to 32.1 kDa, and degree of substitution (SD) ranging from 49 to 62% were prepared. In vitro cytotoxicity data suggest that the guanidylation of chitosan did not produce a more cytotoxic material by MTT assay. The effects of chitosan and guanidyl chitosan on the 14C-mannitol flux across the Caco-2 cell monolayers were evaluated at pH 5.5 and 7.4 at a concentration of 1 mg/ml. Guanidyl chitosan samples were able to promote the transepithelial 14C-mannitol flux at pH 5.5 and 7.4 while their chitosan peers failed. TEER measurements taken on the Caco-2 cell monolayers largely corroborated the 14C-mannitol transport data, and potential for application as an absorption enhancer in vitro.