石菖蒲挥发油-丹参酮ⅡA复合纳米乳的制备、抗肿瘤活性及药动学研究  

Preparation,antitumor activity,and bioavailability of volatile oil of Acorus tatarinowii-TanshinoneⅡA composite nanoemulsion

作　　者：方亮 程红艳 陈卫东 彭灿 张彩云 FANG Liang;CHENG Hong-yan;CHEN Wei-dong;PENG Can;ZHANG Cai-yun(Anhui Key Laboratory of Pharmaceutical Preparation Technology and Application,School of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012;Engineering Technology Research Center of Modern Pharmaceutical Preparations,Education Bureau of Anhui,Hefei 230012;Collaborative Innovation Center for Anhui Genuine Chinese Medicinal Materials Quality Improvement,Hefei 230012;Engineering Technology Research Center for Modern Pharmaceutical Preparation,Hefei 230012)

机构地区：[1]安徽中医药大学药学院药物制剂技术与应用安徽省重点实验室,合肥230012 [2]安徽省教育厅现代药物制剂工程技术研究中心,合肥230012 [3]安徽省道地中药材品质提升创新协同中心,合肥230012 [4]中药复方安徽省重点实验室,合肥230012

出　　处：《中南药学》2023年第6期1441-1447,共7页Central South Pharmacy

基　　金：安徽省科技重大专项项目(No.202203a07020031);安徽省教育厅基金项目(No.KJ2021ZD0065)。

摘　　要：目的联合纳米乳和石菖蒲挥发油(VOA)“引药上行”作用制备VOA-TanⅡA复合纳米乳(VOA-TanⅡA NE),提高丹参酮ⅡA(Tan)的抗肿瘤活性和生物利用度。方法通过伪三元相图确定VOA-TanⅡA NE的最优处方;测试VOA-TanⅡA NE的粒径、电位、形貌及体外释放情况;采用CCK8法探究VOA-TanⅡA NE体外抗脑胶质瘤(C6)能力及血脑屏障下对C6细胞的抑制作用。药动学实验评价VOA-TanⅡA NE的生物利用度。结果处方优化得VOA-TanⅡA NE的粒径和多分散系数分别为(28.90±2.01)nm和(0.14±0.04),包封率为(96.58±0.26)%,呈分散均匀的球形。VOA-TanⅡA NE的体外释放呈缓释效果,同时显著抑制C6细胞生长(其IC_(50)值为TanⅡA的0.18倍)。药动学结果显示VOA-TanⅡA NE的AUC_(0~t)较TanⅡA提高了2.57倍。结论VOA-TanⅡA NE有效提高了TanⅡA体外抗肿瘤作用和体内生物利用度,有望成为TanⅡA脑部递送的新型纳米制剂。Objective To prepare volatile oil of Acorus tatarinowii-TanshinoneⅡA composite nanoemulsion(VOA-TanⅡA NE)by combining the advantages of nanoemulsion and“up-priming”effect of volatile oil of Acorus tatarinowii,and improve the anti-tumor activity and bioavailability of TanshinoneⅡA(TanⅡA).Methods The optimal prescription of VOA-TanⅡA NE was determined by pseudo ternary phase diagram.The particle size,potential,morphology,and release of VOA-TanⅡA NE were measured.The in vitro anti-glioma(C6)ability of VOA-TanⅡA NE and its inhibitory effect on C6 cells under the blood-brain barrier was detected by CCK8.The bioavailability of VOATanⅡA NE was evaluated by in vivo pharmacokinetics.Results The prepared VOA-TanⅡA NE was spherical and uniformly dispersed,with a particle size of(28.90±2.01)nm,a polydisperse index of(0.14±0.04),and an encapsulation rate of(96.58±0.26)%.In vitro release of VOA-TanⅡA NE showed sustained release effect.The IC_(50)value of VOA-TanⅡA NE on C6 cells was 0.18 times of that of TanⅡA.VOA-TanⅡA NE significantly inhibited the growth of C6 cells under the blood-brain barrier.Pharmacokinetics showed that AUC_(0~t)of VOA-TanⅡA NE was 2.57 times higher than that of TanⅡA.Conclusion VOA-TanⅡA NE may effectively improve the in vitro anti-tumor effect of TanⅡA and in vivo bioavailability,providing a novel nano preparation for brain delivery of TanⅡA.

关 键 词：丹参酮ⅡA 石菖蒲挥发油 纳米乳 抗肿瘤活性 生物利用度 

分 类 号：R283[医药卫生—中药学] R285[医药卫生—中医学]