Carboxy Methyl Modification Of Chitosan And Properties Research Of Self-aggregated Nanoparticles

Chitosan as a type of drug carrier has advantages of biochemistry and economic benefits. However, chitosan is only soluble in acidic aqueous solution, which limits its application. Some special chemical modifications can make chitosan amphiphilic and increase its solubility, so as to expand the application range of the chitosan drug delivery system. This paper has carried on the carboxymethyl modification on chitosan and some experiments on preparation of chitosan self-assembled nanoparticles. Doxorubicin hydrochloride as a model drug was used to evaluate the loading effects and drug release profiles of nanoparticles, which could provide theoretical basis and technical supports on the preparation and apply of chitosan self-assembled nanoparticles.As a result, activated chitosan (CS) and chloroacetic acid were reacted under50℃in alkaline condition for3h, and carboxymethyl chitosan--NOCMS was made. Infrared spectrum and Nuclear magnetic resonance hydrogen spectrum identified the structure and replace position of NOCMS, which proved that C2-NH2and C3-OH、C6-OH terminals of CS had been replaced. The yield of synthetic NOCMS was79.48%, the substitution degree was1.3and the content of free amino was40.13%, the isoelectric point was near2.79. Compared with CS, NOCMS greatly increased the solubility in neutral and alkaline solution.CS with positive charges and NOCMS with negative charges could form the self-assembled nanoparticles in neutral aqueous solution by ion gel effect. As a result, it was found that the ideal nanoparticles were prepared under the conditions of concentration ratio1:1(mg/mL), reaction time60min, reaction speed1000rpm. The mean diameter and PDI of nanoparticles were143.7±1.2nm and0.154±0.029respectively, and the surface zeta charge achieved to+37.4mV. Infrared spectrum found that nanoparticles had the structure of-COO-, and hollow core-shell structure could be seen under transmission electron microscope (TEM). We found that the nanoparticles were stable under different time and ion concentrations; however the conditions of pH lower than4could influence the nanoparticles. In the antibacterial experiment, NOCMS-CS nanoparticles showed antibacterial properties to Staphylococcus aureus.Doxorubicin hydrochloride was used as a model antitumor drug, the loading effects and release action from nanoparticles were researched in this report. The mean diameters of DOX loaded nanoparticles could reach237±12nm, and surface zeta potential charge was+31.7 mV. Under TEM, hollow structure of the nanoparticles disappeared, instead, most part of drug packaged in the interior of the nanoparticles, and the entrapment efficiency and drug-loading efficiency reached70.38%and63.14%, respectively. The control-release effect of drug was also found,53.98%of drug was released in preceding12h, after then, the speed slowed down,21.85%of drug was released. The reaction was stable under96h, and77.96%of drug was released at last.