负载α-常春藤皂苷聚合物胶束的制备与体内外评价  

Preparation and evaluation in vitro and in vivo of α -hederin-loaded polymer micelles

作　　者：王慧弟 张金坤[2] 郭进 WANG Huidi;ZHANG Jinkun;GUO Jin(Department of Pharmacy,Wuhan Orthopaedic Hospital of Integrated Traditional Chinese and Western Medicine(Affiliated Hospital of Wuhan Sports University),Wuhan 430070,China;Department of Pharmacy,Yichang Central People's Hospital,Yichang 443008,China;Department of Pharmacy,Traditional Chinese Medicine Hospital of Shiyan City,Shiyan 442012,China)

机构地区：[1]武汉中西医结合骨科医院(武汉体育学院附属医院)药学部,湖北武汉430070 [2]宜昌市中心人民医院药学部,湖北宜昌443008 [3]十堰市中医医院药剂科,湖北十堰442012

出　　处：《药物评价研究》2024年第1期123-129,共7页Drug Evaluation Research

摘　　要：目的 制备α-常春藤皂苷(α-Hed)聚合物胶束(α-Hed-PMs),并评价其对HepG2细胞的抑制效果。方法 以Pluronic F127和TPGS作为载体材料,采用溶剂蒸发-薄膜水化分散法将α-Hed制备成α-Hed-PMs,通过对粒径分布、Zeta电位和包封率进行综合评估确定α-Hed-PMs的处方组成;测定α-Hed-PMs的临界胶束浓度;在透射电镜下观察α-Hed-PMs的微观形貌;通过差示扫描量热法(DSC)判断α-Hed在胶束中的存在状态;考察α-Hed-PMs在pH 5.0、6.0、7.4缓冲液中的稀释稳定性及释药速率;比较α-Hed原料药和α-Hed-PMs(4、8、16、32、64μg·mL^(-1))对HepG2细胞的体外抑制作用;制备HepG2细胞荷瘤小鼠,考察股静脉注射0.9%氯化钠溶液(对照组)、α-Hed和α-Hed-PMs(给药剂量均为30 mg·kg^(-1))对肿瘤体积的影响。结果 α-Hed-PMs的最优处方组成:Pluronic F127和TPGS质量比为6∶1,所形成的聚合物胶束临界胶束浓度为0.031 mg·mL^(-1);在透射电镜下可观察到α-Hed-PMs呈类球形分布;DSC测定结果显示α-Hed在胶束中以非结晶形式存在;α-Hed-PMs经pH 5.0、6.0、7.4缓冲液稀释后,在24 h内均未出现絮凝或沉淀,粒径也基本未发生改变;α-Hed原料药4 h基本释放完全,α-Hed-PMs在不同pH值缓冲液中均为前期药物释放较快,后期药物释放平缓,在50 h基本释放完全;体内外实验结果显示α-Hed-PMs对HepG2细胞的抑制作用均优于α-Hed原料药。结论 以Pluronic F127和TPGS作为载体材料将α-Hed制备成α-Hed-PMs,可达到更好的抗肿瘤效果。Objective To prepareα-hederin-loaded polymer micelles(α-Hed-PMs)and evaluate its inhibition effect on HepG2 cells.Methods Theα-Hed-PMs were prepared by solvent evaporation-thin film hydration dispersion method using Pluronic F127 and TPGS as carrier materials.The formulation composition ofα-Hed-PMs was determined by comprehensive evaluation of particle size distribution,Zeta potential and encapsulation efficiency.The critical micelle concentration of polymer micelles was determined.The microstructure ofα-Hed-PMs was observed under transmission electron microscope.The presence status ofα-Hed in micelles was determined by DSC.The stability and drug release rate ofα-Hed-PMs in medium solution with different pH values(5.0,6.0 and 7.4)were investigated.The inhibition effect ofα-Hed andα-Hed-PMs(4,8,16,32,and 64μg·mL^(−1))were compared in vitro and in vivo.HepG2 tumor bearing mice were prepared,and the effects of 0.9%sodium chloride solution(control group),α-Hed andα-Hed-PMs(dose of 30 mg·kg^(−1))on tumor volume were investigated.Results The optimal composition ofα-Hed-PMs was as follows:the mass ratio of Pluronic F127 to TPGS was 6∶1.The critical micelle concentration was 0.031 mg·mL^(−1).The spherical distribution ofα-HedPMs could be observed under transmission electron microscope.The results of DSC showed thatα-Hed existed in amorphous form in micelles.After dilution with pH 5.0,6.0,and 7.4 buffer solutions,α-Hed PMs showed no flocculation or precipitation within 24 hours,and their particle size remained largely unchanged.Theα-Hed raw material was basically completely released within four hours,the drug release rate ofα-Hed-PMs in different pH values was faster in the early stage and gentle in the late stage,with almost complete release after 50 hours.The results of in vivo and in vitro showed thatα-Hed-PMs had better inhibitory effect on HepG2 cells thanα-hederin.Conclusion In this study,α-Hed was prepared into polymer micelles using Pluronic F127 and TPGS as carrier materials,which

关 键 词：α-常春藤皂苷 聚合物胶束 临界胶束浓度 抑瘤效果 HEPG2细胞 

分 类 号：R943[医药卫生—药剂学]