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目的:制备含DiR碘化物荧光染料的长循环脂质体(DiR-SSL),采用SD大鼠和BALB/c裸鼠进行荧光成像的体内靶向性研究,利用空白SSL包封含5-羧基荧光素(5-FAM)的鳖甲肽(HGRFG-5-FAM,HF)制备HGRFG-5-FAM-SSL(HFL),研究HF及HFL分别给药于大鼠的药代动力学。方法:采用薄膜分散法制备DiR-SSL及HFL,取2组SD大鼠分别尾静脉注射HF及HFL,其HF质量浓度及剂量一致,于不同时间点采血,利用多功能微孔板检测仪分析HF血药浓度,计算药代动力学参数;将DiR-SSL尾静脉注射于BALB/c裸鼠,分别于1,2,5,7,24 h活体成像,读取荧光强度值;取正常SD大鼠尾静脉注射DiR-SSL,24 h后解剖心、肝、脾、肺、肾于荧光成像系统成像并读取荧光强度值,将肝组织冷冻切片进行激光共聚焦扫描。结果:HF注射到SD大鼠体内,其半衰期(T_(1/2))仅0.826 h,而HFL在相同剂量下,T1/2和药时曲线下面积(AUC_(0-∞))分别为HF的16.253,11.899倍;在BALB/c裸鼠活体成像中,荧光主要集中于肝脏位置,随着时间增加荧光强度逐渐减弱;SD大鼠各脏器中的DiR-SSL荧光在肝脏中最强,注射24 h后DiR-SSL仍能在肝脏储留。结论:SSL递药系统能显著延长HF在SD大鼠体内的T_(1/2)。SSL递药系统具有肝靶向作用,提示该系统可作为药物载体进行肝靶向递药。
OBJECTIVE: To prepare long-circulating liposomes (DiR-SSL) containing DiR iodide fluorescent dyes and to study the targeting of fluorescence imaging in vivo using SD rats and BALB / c nude mice. HGRFG-5-FAM-SSL (HFL) was prepared using 5-FAM turtle peptide (HGRFG-5-FAM, HF) to study the pharmacokinetics of HF and HFL administered to rats. Methods: DiR-SSL and HFL were prepared by thin-film dispersion method. Two groups of SD rats were injected with tail vein HF and HFL respectively. The concentrations of HF and HFL were the same. The blood samples were collected at different time points and analyzed by multi-functional microplate detector HF blood concentration was calculated and the pharmacokinetic parameters were calculated. DiR-SSL tail vein was injected into BALB / c nude mice and biopsied at 1,2,5,7,24 h respectively. Fluorescence intensity was measured. Normal SD DiR-SSL was injected into the tail vein of rats. After 24 h, the heart, liver, spleen, lung and kidney were imaged in a fluorescence imaging system and the fluorescence intensity values were read. The liver tissues were frozen and sectioned for confocal laser scanning. Results: The half-life (T 1/2) of HF injected into SD rats was only 0.826 h, while the area under the curve of T1 / 2 and the time-course curve of HFL (AUC 0- ∞) HF, 16.253 and 11.899 times higher than that of HF group. In vivo imaging of BALB / c nude mice, the fluorescence was mainly localized in the liver and the fluorescence intensity gradually weakened with time. The DiR-SSL fluorescence in each organ of SD rats was the strongest in the liver DiR-SSL remained in the liver after 24 h of injection. Conclusion: SSL delivery system can significantly prolong the T_ (1/2) of HF in SD rats. SSL drug delivery system with liver targeting, suggesting that the system can be used as a drug carrier for liver-targeted drug delivery.