Synthesis of a novel amphiphilic quaternized chitosan and its distribution in rats

J Biomater Sci Polym Ed. 2011;22(9):1115-30. doi: 10.1163/092050610X500561.

Abstract

A novel amphiphilic chitosan derivative, N-[(2-hydroxy-3-N,N-dimethylhexadecyl ammonium)propyl]chitosan chloride (N-CQCs), was prepared with a degree of substitution (DS) of 15.58%. N-CQCs was positively charged and its zeta potential was +28.4 mV. The introduction of a long carbon chain with a quaternary ammonium salt group into the chitosan backbone enabled N-CQCs to be lipotropic and hydrophilic. According to the hypothesis of the hypocholesterolemic effect of N-CQCs, its organ distribution in rats was investigated 48 h after administration via gavage using fluorescein isothiocyanate labeling. N-CQCs showed lower cytotoxicity. The plasma half-life of N-CQCs in rats was 48 h and the plasma AUC0-48 h (P) was 371.70 μg/ml per h, suggesting that N-CQCs remained in body for a long time. The results also showed that the accumulation in adipose tissue and gastrointestinal tract was higher than in thymus, kidney, liver and spleen at 48 h after administration. It could be presumed that N-CQCs play an important part in the metabolic process of body fat. Adipose tissue and gastrointestinal tract were the probable interaction sites of N-CQCs and body fat.

Keywords: ADIPOSE TISSUE; CYTOTOXICITY; ORGAN DISTRIBUTION; PLASMA CONCENTRATION; QUATERNIZED CHITOSAN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calorimetry, Differential Scanning
  • Cell Survival / drug effects
  • Chitosan / analogs & derivatives*
  • Chitosan / chemical synthesis
  • Chitosan / chemistry
  • Chitosan / pharmacokinetics
  • Chitosan / toxicity
  • Hepatocytes / drug effects
  • Hepatocytes / physiology
  • Male
  • Molecular Structure
  • Rats, Wistar
  • Solubility
  • Solvents / chemistry
  • Spectroscopy, Fourier Transform Infrared
  • Surface-Active Agents / chemical synthesis*
  • Surface-Active Agents / chemistry
  • Surface-Active Agents / pharmacokinetics*
  • Surface-Active Agents / toxicity
  • Temperature
  • Thermography
  • Water / chemistry
  • X-Ray Diffraction

Substances

  • N-((2-hydroxy-3-N,N-dimethylhexadecylammonium)propyl)chitosan chloride
  • Solvents
  • Surface-Active Agents
  • Water
  • Chitosan