Optimized synthesis of O-carboxymethyl-N,N,N-trimethyl chitosan

V Patrulea; Lee Ann Applegate; V Ostafe; O Jordan; G Borchard

doi:10.1016/j.carbpol.2014.12.014

Optimized synthesis of O-carboxymethyl-N,N,N-trimethyl chitosan

Carbohydr Polym. 2015 May 20:122:46-52. doi: 10.1016/j.carbpol.2014.12.014. Epub 2014 Dec 25.

Authors

V Patrulea¹, Lee Ann Applegate², V Ostafe³, O Jordan⁴, G Borchard⁵

Affiliations

¹ School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland; West University of Timisoara, Department of Biology-Chemistry, Pestalozzi 16, Timisoara 300115, Romania; West University of Timisoara, Advanced Environmental Research Laboratories, Oituz 4, Timisoara 300086, Romania.
² University Hospital of Lausanne (CHUV-UNIL), Department of Musculoskeletal Medicine, EPCR/02/ch. Croisettes 22, 1066 Epalinges, Switzerland.
³ West University of Timisoara, Department of Biology-Chemistry, Pestalozzi 16, Timisoara 300115, Romania; West University of Timisoara, Advanced Environmental Research Laboratories, Oituz 4, Timisoara 300086, Romania.
⁴ School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland.
⁵ School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland. Electronic address: Gerrit.Borchard@unige.ch.

PMID: 25817641
DOI: 10.1016/j.carbpol.2014.12.014

Abstract

We present here the synthesis of a highly O-carboxymethylated chitosan derivative. First, an improved protocol for the two-step synthesis of N-trimethyl chitosan (TMC) from chitosan was developed, yielding a maximum degree of quaternization (DQ) of up to 46.6%. Successively, the chitosan derivative O-carboxymethyl-N-trimethyl chitosan (CMTMC) was synthesized from the TMC obtained by applying an optimized synthesis pathway. In contrast to previous reports, the optimized protocol was shown to yield very high rates (>85%) of O-carboxymethylation of CMTMC, as shown by (1)H NMR and heteronuclear single quantum correlation ((1)H-(13)C HSQC). Finally, in vitro cytocompatibility (viability >80%) of the polymer was demonstrated using human fibroblasts.

Keywords: Chitosan; Chitosan (PubChem CID: 21896651); Chitosan derivatives; Chloroacetic acid (PubChem CID: 300); Drug/gene delivery; Formaldehyde (PubChem CID: 712); Formic acid (PubChem CID: 284); Isopropanol (PubChem CID: 3776); Methyl iodide (PubChem CID: 6328); Methylation; Quaternization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Survival / drug effects
Chemistry Techniques, Synthetic
Chitosan / analogs & derivatives*
Chitosan / chemical synthesis
Chitosan / chemistry
Chitosan / toxicity
Fibroblasts / cytology
Fibroblasts / drug effects
Humans
Methylation
Solubility
Water / chemistry

Substances

6-O-carboxymethyl-N,N,N-trimethyl chitosan
Water
Chitosan