摘要
目的:本研究以聚乙二醇2000(PEG2000)为载体制备番荔辛纳米混悬剂(K19 NPs),对其体外理化性质进行考察,并联合儿茶素(EGCG)进行体内外药效评价.方法:以bottom-up法制备K19 NPs,并考察其粒径分布、介质稳定性、包封率与载药量以及体外释放情况;同时采用小鼠乳腺癌4 T1细胞进行体内外抑制作用的评价以及药物在体内分布情况的评估.结果:本研究制备得到K19 NPs平均粒径为(231.1±1.967)nm,于葡萄糖溶液介质中能够稳定存在,同时载药量和包封率分别可达67.81%和87.99%,且于磷酸盐缓冲液(PBS)中96 h能够累积释放91.5%.体外细胞毒性实验中,可以证明K19 NPs与EGCG联合应用,对于乳腺癌4 T1细胞具有协同抑制作用,抑制强度能够达到K19 NPs的2.26倍.体内研究表明,K19 NPs-EGCG(0.15 mg·kg^(-1)+2 mg·kg^(-1))瘤内注射组肿瘤生长及肺部转移抑制效果最佳(抑瘤率:73.81%;肺转移结节数:1),明显优于市售紫杉醇注射液组以及K19 NPs尾静脉注射组,且相较于静脉注射给药方式具有更集中的肿瘤分布.结论:K19 NPs的成功制备与联合EGCG进行局部给药后对于肿瘤的有效抑制,为其向肿瘤治疗的临床应用转化提供了依据.
Objective:To prepare squamocin nanoparticles(K19 NPs)with PEG2000 as the carrier,investigate its physical and chemical properties in vitro,and evaluate the efficacy of K19 NPs combined with epigallocatechin gallate(EGCG)in vivo and in vitro.Methods:K19 NPs were prepared by bottom-up method,and the particle size distribution,medium stability,entrapment efficiency,drug loading,and release in vitro were investigated.At the same time,mouse 4 T1 breast cancer cells were used to evaluate the inhibitory effect in vivo and in vitro and the distribution of the drug in vivo.Results:The average particle size of K19 NPs prepared in this study was(231.1±1.967)nm,which could stably exist in glucose solution and medium.Meanwhile,the drug loading and encapsulation rate were up to 67.81%and 87.99%,respectively,and the cumulative release rate of K19 NPs at 96 h was 91.5%in phosphate buffer solution(PBS).In vitro cytotoxicity experiments proved that K19 NPs combined with EGCG had a synergistic inhibitory effect on 4 T1 breast cancer cells,and the inhibitory intensity was 2.26 times of that of K19 NPs.Studies in vivo showed that K19 NPs-EGCG injection group(0.15 mg·kg^(-1)+2 mg·kg^(-1))had the best inhibition effect on tumor growth and lung metastasis(tumor inhibition rate:73.81%;number of pulmonary metastatic nodules:1),significantly better than the commercial paclitaxel injection group and K19 NPs tail vein injection group,and had more concentrated tumor distribution compared with intravenous administration.Conclusion:The successful preparation of K19 NPs and effective inhibition of tumor after local administration with EGCG provide a basis for the transformation of K19 NPs on clinical tumor therapy.
作者
王琢
马宏伟
王向涛
WANG Zhuo;MA Hong-wei;WANG Xiang-tao(Heilongjiang University of Chinese Medicine,Harbin 150040,China;Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences/Peking Union Medical College,Beijing 100193,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2022年第8期795-801,共7页
Chinese Journal of New Drugs
基金
中国医学科学院医学与健康创新工程项目(2016-12M-1-012)。
关键词
番荔辛
儿茶素
乳腺癌
纳米混悬剂
squamocin
epigallocatechin gallate
breast cancer
nano suspensions
作者简介
王琢,女,硕士研究生,主要从事药物新剂型研究。联系电话:(010)57833264,E-mail:773935370@qq.com;通讯作者:王向涛,男,研究员,博士生导师,主要从事药物新剂型研究。E-mail:xtaowang@163.com。
