Abstract: The aims of this study were to obtain a safe and stable composite micelle using N-octyl-N-quaternary ammonium chitosan (NTMC) coating with sodium carboxymethyl cellulose (CMCNa).NTMC was synthesized and its critical micelle concentration was measured.NTMC micelles were prepared by ultrasonic dialysis;its drug loading efficiency and drug encapsulation efficiency were determined by HPLC.The composite micelle NTMC/CMCNa was prepared by absorption of CMCNa on the NTMC micelles.The effects of CMCNa-coating on morphology,particle size,Zeta potential,cytotoxicity and hemolysis of micelles were studied.It was found that NTMC with (37.5±3.6)% N-octyl substitution and 48.4% N-trimethyl substitution exhibited a low critical micelle concentration at 35.6 μg/mL.The particle size of NTMC micelles was (224.6±8.4) nm,Zeta potential was +(44.7±4.5) mV and a spherical shape was observed under AFM.The drug loading efficiency of NTMC micelles to paclitaxel was up to (40.2±2.2 )%,with the drug encapsulation efficiency of (34.4±1.7 )%.The particle size of NTMC/CMCNa micelles was (302.4±27.3) nm,the Zeta potential was -(37.4±6.2) mV and they showed a slightly irregular spherical shape.Compared with NTMC micelles,NTMC/CMCNa micelles exhibited a decreased cytotoxicity and hemolysis.In conclusions,NTMC micelles exhibited the significant solubilizing effect for insoluble drugs,such as paclitaxel.By the coating of CMCNa,the strong positive charge of NTMC micelles can be shieled to improve the safety of the micelles.