摘要
目的制备长春新碱固体脂质纳米粒(VCR-SLN),建立反相高效液相色谱法测定长春新碱血药浓度,研究大鼠体内VCR-SLN药动学过程;并观察VCR-SLN体外抗肿瘤作用。方法采用复乳溶剂挥发法制备VCR-SLN。取12只健康SD大鼠,雌雄各半,分为两组,分别尾静脉给予VCR-SLN和长春新碱水溶剂(VCR-Sol),剂量为1.2 mg·kg-1,采用高效液相色谱法测长春新碱血药浓度,并用3P97药动学软件进行数据处理。MTT法考察VCR-SLN抗体外培养人乳腺癌MDA-MB-231细胞增殖作用。结果 VCR-SLN和VCR-Sol的体内药动学过程均符合二室模型,t蚝虔α分别为(11.57±1.15)、(4.99±0.95)min;t蚝虔β分别为(1 377.57±72.39)和(170.04±14.28)min,AUC0-∞分别为(492.90±52.37)和(74.68±9.46)μg·min·mL-1,CL分别为(0.68±0.04)和(4.86±0.86)mL·min-1。体外抗肿瘤作用结果表明,VCR-SLN及VCR-Sol对人乳腺癌MDA-MB-231细胞的IC50分别为(0.012±0.001)和(0.126±0.007)μg·mL-1。结论与VCR-Sol相比,VCR-SLN经注射给药后,体内消除相对缓慢,滞留时间延长,呈现缓释效果。VCR-Sol与VCR-SLN对人乳腺癌MDA-MB-231细胞增殖均有明显的抑制作用,并且VCR-SLN的抑制作用强于VCR-Sol。
AIM To study the pharmacokinetics of vincristine solid lipid nanoparticles （VCR-SLN） in rats by HPLC method, and evaluate the effects of VCR-SLN on tumorigenesis in MDA-MB-231 cell. METHODS VCR-SLN was prepared by multiple emulsion-solvent diffusion technique. Twelve SD rats were divided into two groups （n = 6, 3 males and 3 females）, and were received VCR-SLN and vincristine sulfate solution （VCR- Sol） at the same dosage of 1.2 mg＇kg-1 via tail intravenous injection, respectively. The plasma concentrations of VCR were determined by HPLC, and the pharmacokinetic parameters were calculated by 3P97 software. Human MDA-MB-231 cells were treated with VCR-SLN, and the effects on ceils inhibition were investigated by MTF cell viability assay. RESULTS The study of pharmacokinetics of VCR-SLN and VCR-Sol in rats showed the two preparations were fitted with two-compartment model, and t＋~ were （11.57 ＋ 1.15） min and （4.99 _＋ 0.95） rain, t~~ were （1 377.57 _＋ 72.39） rain amt （170.04 ＋_ 14.28） rain, AUC0_~ were （492.90 ＋ 52.37） txg＇min＂ mL ~ and （74.68 ＋ 9.46） ~g.min＇mL-1, CL were （0.68 ＋ 0.04） mL＇min-j and （4.86 ＋ 0.86） mL＇min-1, respectively. Growth of MDA-MB-231 cells were inhibited obviously by VCR-SLN and VCR-Sol, the VCR-SLN group showed greater effects than VCR-Sol group. CONCLUSION VCR-SLN shows a significant sustained- release and lower excretion eharacteristics in vivo. Furthermore, VCR-SLN shows a greater effeet on inhibiting the growth of MDA-MB-231 cells eompared with VCR-Sol group.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2013年第12期965-969,共5页
Chinese Journal of New Drugs and Clinical Remedies
关键词
长春新碱
脂质体
纳米粒子
药动学
抗肿瘤
体外
vincristine
liposomes, nanoparticles
pharmacokinetics
anti-tumor, in vitro
