阿霉素白蛋白透明质酸纳米粒的制备及评价  

Preparation and evaluation of albumin and hyaluronic acid nanoparticles loaded with doxorubicin

作　　者：陶静[1] 李黎[1] 廖蓉惠 涂娜 沈雪 Tao Jing;Li Li;Liao Ronghui;Tu Na;Shen Xue(Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of Pharmacy,Chengdu University,Chengdu 610106)

机构地区：[1]抗生素研究与再评价四川省重点实验室,四川抗菌素工业研究所,药学院,成都大学,成都610106

出　　处：《中国抗生素杂志》2023年第8期921-929,共9页Chinese Journal of Antibiotics

摘　　要：目的制备以人血清白蛋白(human serum albumin,HSA)和透明质酸(hyaluronic acid,HA)为载体,负载抗肿瘤药物阿霉素(doxorubicin,DOX)的纳米粒子,对纳米粒制备处方进行优化,并对制剂进行质量评价,初步考察纳米粒的体外抗肿瘤效果。方法采用去溶剂-交联法制备得到负载阿霉素的白蛋白透明质酸纳米粒子(DOX-HSA-HA NPs),并利用Box-Behnken Design响应面优化筛选最优处方,采用透射电镜、激光粒度仪对纳米粒的形貌和粒径进行考察,并考察纳米粒的体外释放效果及体外溶血情况,最后通过细胞毒性实验初步考察纳米粒的体外抗肿瘤效果。结果按优化条件制得的DOX-HSA-HA NPs透射电镜下呈球形,分布均一,粒径为(213.39±0.79)nm,PDI值为0.062±0.012,Zeta电位为-25.53 mV,包封率达88.85%,载药量达2.06%;体外释放结果表明,在pH 6.8和pH 7.4条件下DOX-HSA-HA NPs具有缓释效果,加入透明质酸酶之后,DOX的释放量增加;溶血性实验表明,纳米载体材料HSA-HA NPs无溶血风险,可用于静脉注射给药;体外细胞实验表明,空白载体对细胞基本无毒性,相比于DOX-HSA NPs,DOX-HSA-HA NPs对小鼠乳腺癌4T1细胞的细胞毒性增强。结论采用去溶剂-交联法制得的DOX-HSA-HA NPs分布均匀,包封率高,具有明显的缓释作用和增强的细胞毒性。Objective In order to improve the efficiency of cancer treatment,doxorubicin(DOX)-loaded Human Serum Albumin(HSA)and Hyaluronic acid(HA)nanoparticles(abbreviated as DOX-HSA-HA NPs)were prepared and optimized.Then,the drug properties and antitumor activity were evaluated.Methods The DOX-HSA-HA NPs was prepared by the solvent removal and crosslinking method.Then,the Box-Behnken design response surface methodology was used to optimize the initial prescription.In addition,the morphology of the nanoparticles was investigated by transmission electron microscope(TEM),and the size distribution of the nanoparticles was determined by ZetaPlus particle size and zeta potential analyzer.Moreover,the release behavior of the nanoparticles in vitro was investigated by dialysis,and the hemolysis in vitro was investigated using healthy rats.Finally,the anti-tumor effect of the nanoparticles in vitro was preliminarily investigated by cytotoxicity assays.Results The DOX-HSA-HA NPs prepared under the optimized conditions were spherical and uniformly distributed,with a particle size of(213.39±0.79)nm,a PDI of 0.062±0.012,and a Zeta potential of-25.53 mV.The encapsulation rate and drug loading capacity of DOX were 88.85%and 2.06%.In vitro release results showed that DOX-HSA-HA NPs had a sustained release effect at pH 6.8 and pH 7.4,and the DOX release rate increased when treated with hyaluronidase.The hemolytic test showed that the nanocarrier materials HSA-HA NPs were safe and non-toxic,and were suitable for intravenous administration.Cytotoxicity assay showed that HSA-HA NPs were nontoxic to 4T1 cells(mouse breast cancer cells),and DOX-HSA-HA NPs were more cytotoxic to 4T1 cells than DOX-HSA NPs.Conclusion The DOX-HSA-HA NPs prepared by the solvent removal and crosslinking method exhibited uniform particle size and size distribution,high encapsulation efficiency,a sustained drug release behavior,and showed enhanced cytotoxicity.

关 键 词：人血清白蛋白 透明质酸 阿霉素 纳米粒 体外抗肿瘤 

分 类 号：R978.1[医药卫生—药品]