摘要
目的:制备雷公藤红素(celastrol,CEL)纳米胶束,并对其进行表征和体外细胞毒性作用评价。方法:合成透明质酸-聚乙二醇-壳聚糖-油酸(hyaluronic-acid-polyethylene-glycol-chitosan-oleic-acid,HA-mPEG-CS-OA)聚合物,采用核磁共振氢谱、傅里叶变换红外光谱确证合成聚合物的结构。以HA-mPEG-CS-OA为载体,采用透析法制备包载CEL的纳米胶束(HAmPEG-CS-OA/CEL)。在单因素试验结果基础上,以包封率、载药量和粒径的综合评分为指标,CEL的投药量、水化体积、超声时间为因素,采用正交试验L9(3~4)优选处方工艺。以CCK-8法检测CEL和HA-mPEG-CS-OA/CEL对人肝癌细胞HepG2、人肺腺癌细胞A549和人宫颈癌细胞HeLa的增殖抑制率,并选择三者中最敏感细胞进行细胞摄取实验。结果:成功合成HAmPEG-CS-OA聚合物,其形态呈类圆形,大小均一,粒径为(227.8±8.6) nm,包封率为(82.33±0.90)%,载药量为(2.47±0.03)%。CCK-8法检测结果表明HA-mPEG-CS-OA/CEL对HeLa细胞最敏感,细胞摄取实验验证经透明质酸修饰后可以增加HeLa细胞对聚乙二醇-壳聚糖-油酸的摄取。结论:制备HA-mPEG-CS-OA/CEL纳米胶束,其具有显著的体外抗肿瘤作用。
OBJECTIVE To prepare celastrol(CEL)-loaded nanomicelles,characterize their physicochemical properties,and evaluate their in vitro cytotoxicity.METHODS A hyaluronic-acid-polyethylene-glycol-chitosan-oleic-acid conjugate(HA-mPEG-CS-OA)was synthesized.Its structure was confirmed by nuclear magnetic resonance(NMR)and Fourier-transform infrared(FTIR)spectroscopy.CEL-loaded nanomicelles(HA-mPEG-CS-OA/CEL)were prepared by a dialysis method using HA-mPEG-CS-OA as the carrier.Guided by single-factor experiments,an L(934)orthogonal design was used to optimize the for⁃mulation,with a composite score based on encapsulation efficiency(EE),drug loading(DL),and particle size as the response.Factors included CEL feed amount,hydration volume,and sonication time.Cytotoxicity of CEL and HA-mPEG-CS-OA/CEL was assessed by the CCK-8 assay in HepG2(human hepatoma),A549(human lung adenocarcinoma),and HeLa(human cervical cancer)cells.The most sensitive cell line was then used for cellular uptake studies.RESUITS The HA-mPEG-CS-OA carrier was successfully synthesized.The resulting CEL-loaded micelles were spherical and uniform,with a mean particle size of(227.8±8.6)nm,EE of(82.33±0.90)%,and DL of(2.47±0.03)%.CCK-8 assays indicated that HA-mPEG-CS-OA/CEL exhibited the greatest cytotoxic effect in HeLa cells among the three tested lines.Cellular uptake experiments confirmed that hyaluronic acid modification enhanced HeLa uptake of mPEG-CS-OA micelles.CONCLUSION HA-mPEG-CS-OA/CEL nanomicelles were successfully prepared and demonstrated significant in vitro antitumor activity.
作者
王雪
刘喜纲
王汝兴
梁彬彬
唐世英
WANG Xue;LIU Xigang;WANG Ruxing;LIANG Binbin;TANG Shiying(Chengde Medical University/Hebei Key Laboratory for Research and Development of Chinese Medicine,Hebei Chengde 067000,China)
出处
《中国医院药学杂志》
北大核心
2025年第23期2675-2683,共9页
Chinese Journal of Hospital Pharmacy
基金
河北省高等学校科学技术研究项目(编号:ZD2022121)。
