The current view on biological potency of cationically modified chitosan

Area of Science:

• Biochemistry
• Polymer Science
• Pharmacology

Background:

• Chitosan, a biocompatible polymer derived from chitin, is widely studied for its biological effects.
• Cationically modified chitosan, specifically N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), was synthesized for enhanced properties.

Purpose of the Study:

• To review and compare the biological effects of chitosan with its novel derivative, HTCC.
• To investigate the unique beneficial properties of HTCC, including heparin binding, absorption, distribution, and effects on blood parameters and cholesterol levels.

Main Methods:

• Synthesis of HTCC via covalent attachment of glycidyltrimethylammonium chloride (GTMAC).
• Comparison of biological effects between chitosan and HTCC.
• In vivo studies in C57BL/6j mice using FITC-labeled HTCC to assess absorption and distribution.
• In vivo studies in apoE-knockout mice to evaluate effects on cholesterol levels.
• In vitro studies with HepG2 cells to investigate effects on HMG-CoAR mRNA levels.

Main Results:

• HTCC exhibits similar biological effects to chitosan but possesses unique properties, such as heparin binding at physiological pH.
• Oral administration of FITC-labeled HTCC in mice showed rapid absorption (within 1 hour) and distribution to lung, heart, and kidneys.
• HTCC stimulates platelet aggregation, decreases red blood cell (RBC) deformability, and appears to reduce plasma total cholesterol and LDL-cholesterol levels in apoE-knockout mice.
• HTCC may down-regulate HMG-CoAR mRNA levels in HepG2 cells in vitro.

Conclusions:

• HTCC demonstrates promising unique biological properties beyond those of native chitosan.
• Its rapid absorption, distribution, and potential cholesterol-lowering effects warrant further investigation for therapeutic applications.
• HTCC's impact on blood cell aggregation and deformability suggests further research into its cardiovascular effects is needed.