经肝动脉灌注人血白蛋白-索拉非尼纳米粒联合明胶海绵颗粒栓塞治疗在兔VX2肝癌模型中的实验研究  

Experimental study on HSA-SRF-NPs combined with gelatin sponge particles by transarterial chemoembolization in rabbit VX2 liver tumor model

作　　者：高文慧 陈志军 简晓顺 陈国硕 GAO Wenhui;CHEN Zhijun;JIAN Xiaoshun;CHEN Guoshuo(Department of Pharmacy,Affiliated Cancer Hospital&Institute of Guangzhou Medical University,Guangdong Guangzhou 510095,China;Medical Imaging Department,Affiliated Cancer Hospital&Institute of Guangzhou Medical University,Guangdong Guangzhou 510095,China;Department of Interventional Radiology,Affiliated Cancer Hospital&Institute of Guangzhou Medical University,Guangdong Guangzhou 510095,China)

机构地区：[1]广州医科大学附属肿瘤医院药学部,广东广州510095 [2]广州医科大学附属肿瘤医院影像科,广东广州510095 [3]广州医科大学附属肿瘤医院介入科,广东广州510095

出　　处：《中国医院药学杂志》2023年第21期2373-2378,共6页Chinese Journal of Hospital Pharmacy

基　　金：广东省中医药局面上项目(编号:20231234);广州市基础研究计划基础与应用基础研究项目(编号:202102021196);广东省颐养健康慈善基金会项目(编号:JZ2022020)。

摘　　要：目的:探讨经肝动脉灌注人血白蛋白-索拉非尼纳米粒(human serum albumin-sorafenib nanoparticles,HSA-SRF-NPs)联合明胶海绵颗粒栓塞治疗在兔VX2肝癌模型中的药动学、抑制肿瘤增殖能力和肝毒性等,为HSA-SRF-NPs在化疗栓塞治疗中的应用提供实验依据。方法:构建兔肝癌模型并实施明胶海绵颗粒+索拉非尼/HSA-SRF-NPs/生理盐水介入治疗,48 h后收集血浆和组织,高效液相色谱法测定药物含量,绘制药时曲线,考察组织分布特征,并进行肿瘤和肝组织的病理学评价。结果:术前CT扫描证实建模成功。索拉非尼纳米粒组AUC、t1/2、MRT、Cmax、CL和Vd分别为(69.55±13.57)μg·h·mL^(-1)、(7.81±0.96)h、(11.82±0.26)h、(4.49±0.42)μg·mL^(-1)、(111.05±20.89)mL·h^(-1)和(271.30±373.81)mL。索拉非尼纳米粒组肝脏和肿瘤中的药物含量分别是索拉非尼组的2.3倍和2.0倍。抑制肿瘤增殖能力由高到低依次为:索拉非尼纳米粒组>索拉非尼组>生理盐水组,3组中均未见明显的肝毒性。结论:经肝动脉灌注HSA-SRF-NPs能显著延长药物在体内的滞留时间,增加药物在肝脏和肿瘤中浓度,增强抑制肿瘤增殖能力,安全性良好,是一种潜在的肝动脉灌注治疗药物。OBJECTIVE To investigate the pharmacokinetics,antitumor activity,hepatotoxicity and so on of HSA-SRF-NPs combined with gelatin sponge particles by transarterial chemoembolization in rabbit VX2 liver tumor model,so as to provide experimental basis for the application of HSA-SRF-NPs in transcatheter arterial chemoembolization.METHODS The rabbit liver tumor model was implemented transarterial chemoembolization with gelatin sponge particles combined with sorafenib,HSA-SRF-NPs or physiological saline.After 48 hours,plasma and tissues were collected.The drug content was determined by HPLC,the drug-time curve was drawn,the tissue distribution characteristics were analyzed,and the pathology of tumors and liver tissue was evaluated.RESULTS Preoperative CT scan confirmed the modeling success.The AUC,t1/2,MRT,Cmax,CL and Vd of sorafenib nanoparticles group were(69.55±13.57)μg·h·mL^(-1),(7.81±0.96)h,(11.82±0.26)h,(4.49±0.42)μg·mL^(-1),(111.05±20.89)mL·h^(-1) and(271.30±373.81)mL,respectively.The drug content in liver and tumor in sorafenib nanoparticles group was 2.3 times and 2 times higher than that in sorafenib group.The inhibition ability order against tumor proliferation was as follows:sorafenib nanoparticles group>sorafenib group>physiological saline group.There was no obvious hepatotoxicity in the three groups.CONCLUSION By transarterial chemoembolization with HSA-SRF-NPs,the retention time of sorafenib in the body is prolonged,the content of sorafenib in liver and tumor tissue is increased,and the inhibition ability against tumor proliferation is enhanced.It also shows good safety,and is suitable for transcatheter arterial chemoembolization.

关 键 词：索拉非尼 纳米粒 明胶海绵颗粒 肝癌模型 化疗栓塞治疗 

分 类 号：R944[医药卫生—药剂学]