Challenges in evaluation of chitosan and trimethylated chitosan (TMC) as mucosal permeation enhancers: From synthesis to in vitro application.

• Published in: Journal of Controlled Release
• Main Authors: Benediktsdóttir, Berglind Eva, Baldursson, Ólafur, Másson, Már
• Other Authors: Univ Iceland, Sch Hlth Sci, Fac Pharmaceut Sci, IS-107 Reykjavik, Iceland, Landspitali, Dept Pulm Med, IS-101 Reykjavik, Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier Science BV 2014
• Subjects: Öndunarfæri; Lyf; Animals; Chitosan/chemical synthesis; Drug Carriers/chemical synthesis; Humans; Intestinal Mucosa/metabolism*; Respiratory Mucosa/metabolism*; Chitosan/chemistry; Chitosan/metabolism*; Drug Carriers/chemistry; Drug Carriers/metabolism*; Iceland
• Online Access: http://hdl.handle.net/2336/325618

To access publisher's full text version of this article click on the hyperlink at the bottom of the page 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. Eimskip Fund of University of Iceland, University of Iceland Research Fund, Landspitali University Hospital Science Fund, Bergthóra and Thorsteins Scheving Thorsteinssonar Fund