Synthesis of N, N, N-trimethyl chitosan-based nanospheres for the prolonged release of curcumin

Abstract

It is critical to develop a hydrophilic drug carrier with positive charge on the surface to enhance the bioavailability of curcumin to overcome the tissue barrier, e.g., blood brain barrier. In this paper, a quaternized chitosan derivative, N,N,N-Trimethyl Chitosan (TMC) was produced which is a cationic polysaccharide. Nuclear magnetic resonance (¹H-NMR) and Infrared Spectroscopy (FTIR) have been used to verify the synthesis of TMC. A simple nanoemulsion process has been developed to produce TMC-based nanosphere to load curcumin. A high encapsulation efficiency (over 90%) can be observed. The average particle size of nanospheres made of TMC with 2.5 mg/mL and 4.0 mg/ mL is estimated at 555.3±117.7 nm and 771.2±123.2 nm, respectively. The effect of the concentrations of TMC on the release profile has been investigated. It is found that nanospheres made of a higher concentration of TMC, 4.0 mg/mL, could lead to an extended release of curcumin, and the first-order release kinetics can be observed when release time increases from 0 to 265 h. The release kinetics of curcumin loaded in TMC nanospheres is also influenced by pH value. In addition, the cytotoxicity study shows that no toxic effect can be found when cells are treated with synthetic TMC. The relative cell viability of mouse cardiac endothelial cells treated with curcumin loaded TMC nanospheres is higher than that when cells treated with curcumin alone.