title: Challenges in evaluation of chitosan and trimethylated chitosan (TMC) as  mucosal permeation enhancers: From synthesis to in vitro application.
abstract: The polysaccharide chitosan and the water soluble chitosan derivative N,N,N-trimethyl chitosan (TMC) have been widely investigated as permeation enhancers of mucosal surfaces with numerous papers published over the last two decades. Although both chitosan and TMC increase permeation of markers through mucosal membranes, such as the intestinal and airway epithelium as well as in in vivo models, these investigations have not led to their use in marketed drug formulations. In this review, the reported extent of the permeation enhancement and cell viability after chitosan or TMC treatment in intestinal and airway models is critically evaluated and concluded that the apparent discrepancies can be explained by differences in polymer structure, experimental conditions and in vitro models. Additionally, aspects regarding the synthesis of TMC and its structural characterization are described, focusing on new synthetic strategies implemented to reduce O-methylation. Finally recommendations are provided on how studies can be conducted to improve understanding of the structure–activity relationship and elucidate possible mechanism of action.
authors: Berglind Eva
authors: BE
authors: Benediktsdóttir
authors: Ólafur
authors: Ó
authors: Baldursson
authors: Már
authors: M
authors: Másson
mesh_terms: D000818:Animals; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; C118071:N-trimethyl chitosan chloride; D048271:Chitosan