Synthesis of N-fatty acyl-N-trimethyl chitosan and its solubilization on osthole / 中草药

ABSTRACT

Objective: To synthesize two kinds of amphipathic chitosan (CS) derivatives, self-assembling to polymeric micelles as novel drug delivery system. Methods: N-Trimethyl chitosan (TMC) was synthesized by the reaction between CS and CH3I, and long-chain fatty acid was combined to amino group of TMC so as to synthesize the derivative of N-fatty acyl-N-TMC (FA-TMC). The polymer structure was confirmed by FT-IR, 1H-NMR spectra, and element analysis. Then the hydrophobicity drug of osthole (OST) was used as model drug to evaluate the solubilizing ability on those polymeric micelles. Results: Two kinds of six novel CS derivatives were synthesized, the results indicated that the different degrees of quaternisation (DQ) and degrees of substitution (DS) were important parameters to the micelles properties of FA-TMC. To the OST loaded micelles prepared by ultrasonic method, the best candidate materials of the N-palmitoyl-N-TMC (PA-TMC) was the polyer with DQ of 62.00% and DS of 13.37%, while the N-caprinoyl-N-TMC (CA-TMC) was the polyer with DQ of 43.06% and DS of 22.00%. The entrapment efficiency of PA-TMC and CA-TMC were 76.67% and 79.11%, and the drug-loading rates of PA-TMC and CA-TMC were 19.01% and 19.08%, respectively. The solubility of OST increased up to two orders of magnitude in the OST-loaded micelles. Conclusion: FA-TMC is a potential solubilization carrier, self-assembling to polymeric micelles in water, with obvious solubilization on OST, and lays the foundation for the further research and application of OST preparation.