A-Trimethyl chitosan

A-Trimethyl Chitosan as Absorption Enhancer of Peptide Drugs. Ill... 

Sieval, A.B., Thanou, M, Kotze, A.F., Verhoef, J.C., Brussee, J. and Junginger, H.E. (1998) Preparation and NMR-characterization of highly substituted A-trimethyl chitosan hydrochloride. Carbohydr. Polym 36 157-165. 

Thanou, M., Verhoef, J.C. Romeijn, S.G., Nagelkerke, J.F., Merkus, F.W.H.M. and Junginger, H.E. (1999) Effects of A-trimethyl chitosan chloride, a novel absorption enhancer, on Caco-2 intestinal epithelia and the ciliary beat frequency of chicken embryo trachea. Int. J. Pharm. 185 73-82. 

Fig. 2 Synthesis of A/ -trimethyl chitosan and substructure of thiolated chitosan derivatives [28, 29]...

Kotze, A.F. et al. A-trimethyl chitosan chloride as a potential absorption enhancer across mucosal surfaces In vitro evaluation in intestinal epithelial cells (caco-2). Pharm. Res., 14, 1197,1997. 

Thanou, M. et al. A-trimethylated chitosan chloride (TMC) improves the intestinal permeation of the peptide drug buserelin in vitro (caco-2 cells) and in vivo (rats). Pharm. Res., 17, 27, 2000. 

Chitosan-based nano- and microparticles are widely used for fabrication of controlled dmg release systems. Numerous studies have demonstrated that chitosan and its derivatives (A-trimethyl chitosan, mono-A-carboxymethyl chitosan, etc.) are effective and safe for absorption enhance to improve mucosal (nasal, peroral) delivery of hydrophylic macromolecules, such as peptide and protein dmgs as well as heparins [37,38]. This absorption enhancing effect of chitosan is caused by the opening of intercellular tight junctions, thereby favoring the paracellular transport of macro-molecular dmgs. Recently, a series of successful model chitosan-based polymer systems for mucosal dmg delivery have been reported. Thus, Lim et al. [39] have proposed novel polymer microparticles based on combination of hyaluronic acid and chitosan hydroglutamate... 

Sayin, B., S. Somavarapu, X. W. Li, M. Thanou, D. Sesardic, H. O. Alpar, and S. enel. 2008. Mono-lV-carboxymethyl chitosan (MCC) and A-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery. International Journal of Pharmaceutics 363 (1-2) 139-148. 

As previously mentioned, the amino groups are target moieties for the modification of the backbone in order to gain certain additional advantageous properties. For instance, various chitosan derivatives such as chitosan-EDTA conjugates [15], A -trimethylated chitosan [16], mono-A-carboxymethyl chitosan [17] and A-sulfo-chitosan [18] have been introduced in the pharmaceutical field in the last decade. A further modification of chitosan is based on the immobilization of thiol groups, leading to so-called thiolated chitosans (Fig. 1). 

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