Through acylation reaction , a novel chitosan amphiphilic derivative , N,N-dilauryl-3,6-O-mPEG-chitosan (PEDLCS) with high degree of grafting was synthesized by grafting mPEG-COOH onto N,N-dilauryl chitosan. The product was characterized with 1H NMR,FTIR,and EA. KP-loaded PEDLCS micelles were prepared by dialysis. PEDLCS could form micelles via self-assembly in aqueous solution and the CMC value of PEDLCS was 0.1170 mg/mL. The drug loading content and efficiency of KP-loaded PEDLCS micelles were determined as 34.48% and 65.78% respectively under the optimal ratio of KP and PEDLCS (0.8∶1). The KP-loaded PEDLCS micelles had average size of 155.1nm and zeta potential of−31.6 mV. The response experiments about drug-loaded micelle under the conditions of different pH values showed that stability of the micelles decreased and diameter of the micelles increased with decreasing pH value,and the process was reversible. The range of pH response rightly agreed with the growth microenvironment of tumor cell (pH7.2—6.0). It would be expected to become a new material of drug delivery system.%聚乙二醇单甲醚(mPEG)先经过氯乙酸羧化后,再通过酰化反应接枝到双烷基壳聚糖上,制备高接枝度的N,N-双十二烷基-3,6-O-mPEG-壳聚糖(PEDLCS)双亲性衍生物,用1H NMR、FTIR、EA等对产物进行表征,并用透析法制得PEDLCS载酮洛芬(KP)胶束。结果表明,PEDLCS在水溶液中能自组装形成胶束,CMC值为0.1170mg/mL;载药胶束的最优投料比为KP/PEDLCS=0.8∶1,载药量34.48%,包封率65.78%,粒径155.1nm, Zeta电位−31.6mV。载药胶束在不同pH值条件下的响应性实验表明,随着pH值的减小,胶束的稳定性降低,胶束粒径变大,具有可逆性。pH值响应范围符合肿瘤细胞微环境(pH值为7.2~6.0),有望成为具有pH值响应主动靶向的隐形纳米胶束。
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