【摘要】 两亲性聚合物纳米颗粒作为疏水性抗肿瘤药物载体因其能够增强化疗效率并降低毒副作用而受到广泛关注.采用双乳液溶剂挥发法制备了聚(3-羟基丁酸酯-co-3-羟基戊酸酯)(PHBV)/葡聚糖纳米颗粒,测得平均粒径为205.0±6.9nm,Zeta电势为-1.59±0.12mV,纳米颗粒具有明显的壳核结构,粒径均一,分散性良好.将疏水性化疗药物顺铂包载后,其粒径及电势均无明显变化,载药量达19.3±2.9%.顺铂在模拟肿瘤细胞环境pH=5.5的磷酸盐缓冲液(PBS)中比正常细胞环境pH=7.4时释放更快,且累计释放周期均长达7d以上,表明该药物载体具有一定的pH响应性以及优异的缓释性能.细胞集落形成实验表明PHBV/葡聚糖纳米药物载体具有良好的生物相容性,而载药纳米颗粒对肿瘤细胞的毒性明显高于正常细胞,表明该纳米颗粒对肿瘤细胞具有更强的杀伤作用.综上所述,PHBV/葡聚糖纳米颗粒具有两亲性分子结构,合适的粒径及Zeta电势,显著的缓释效果,对肿瘤细胞具有pH响应性及更强的杀伤作用等优势,有望成为一种新型纳米药物载体,在癌症化疗中显著提高药物利用率并降低毒副作用.更多还原

【Abstract】 Amphiphilic polymer nanoparticles have attracted considerable attention especially as anticancer drug delivery system,since they can enhance bioavailability and reduce side effects of drugs used for chemotherapy.Novel poly(3-hydroxybutyric-co-3-hydroxyvaleric,PHBV)/dextran nanoparticles(PDNPs)drug delivery system was formulated via an original double emulsion(w1/o1/w2)solvent-evaporation method.The mean diameter of PDNPs was 205.0±6.9 nm and their zeta potential was-1.59±0.12 mV by using dynamic light scattering(DLS)detection.PDNPs showed obvious core-shell structure with uniform particle dispersion.Cisplatin,as a model anticancer drug,was loaded to demonstrate the characterizations of the drug delivery system,and its loading did not significantly alter the hydrodynamic diameter and zeta potential of nanoparticles with 19.3±2.9% of drug loading content(DLC).In-vitro drug release profile of cisplatin from cisplatin-loaded PDNPs found that it can be released faster in normal cells(pH=7.4)than cancer cells(pH=5.5)in phosphate buffered saline(PBS),and the release period was more than 7 d,which demonstrated that this drug delivery system was pH-responsive and with excellent slow-release performance.PDNPs displayed no cytotoxicity,and cisplatin-loaded PDNPs exhibited higher killing efficient to cancer cells when compared with normal cells,which indicated this nano-delivery system can kill cancer cells more effectively.Thus,the novel PDNPs drug delivery system can be potentially applied for cancer chemotherapy,which will improve the utilization ratio and reduce side effect of drugsin the cancer chemotherapy.更多还原