肝动脉注射阿霉素温度敏感脂质体的靶行为和治疗应用的研究

Temperature sensitive liposome entrapped adriamycin was injected into the hepatic artery of Wistar rats bearing implanted hepatic tumor. Two hours after the injection, the liver was heated to 42 ℃ and maintained at that temperature for 6 minutes using a local hyperthermia. The variation in the pattern of the concentration of the liposomal drug in circulation, and the drug distribution in tissues were investigated. Results indicated that adriamycin was released from the liposomes with the drug concentration peaking in circulation at 30 minutes after heating. Following the hyperthermia treatment, the total amount of drug in the liver decreased, while that in the tumor and urine increased. The ¹⁴C labeled liposome track test showed that a parallel relationship between the lipid and the drug was maintained for 8 hours after the hepatic injection, and physiological environment was a determinant of change and existence of liposomal carrier. However, the drug encapsulated in the liposomes can be controlled by hyperthermia to target the tumor. Therapeutic experiments showed that in the group treated with the hepatic artery- injected liposome plus hyperthermia control, the liver tumor growth of the rats administered at 7 days after W₂₅₆ carcinosarcoma implantation on liver was notably inhibited and the life-span of the animal was greatly extended compared with those of aqueous administration groups and ⅳ injected liposome group.     

肝动脉注射阿霉素温度敏感脂质体的制剂研究

自Yatvin等创造温度敏感脂质体以来,许多研究结果证明它是靶治疗的良好载体。Chuang等认为根据荷瘤肝脏的血流分布,设想将温度敏感脂质体通过肝动脉注射滞留于肝动脉,结合人为控制释放脂质体中所包封的药物,有可能提高肝脏肿瘤中的药物浓     

多糖多相脂质体的药理作用

本文对分别装载环磷酰胺、5-氟脲嘧啶、丝裂霉素C和顺铂等四类化疗药的多糖多相脂质体的抗小鼠移植肿瘤作用,及其对小鼠免疫器官、外周血白细胞和蛋白质合成的影响进行了初步研究。同时测定了装载丝裂霉素的该类脂质作的LD_(50)。证明了多糖多相脂质体具有增强化疗药的抗肿瘤作用。降低药物毒性,促进蛋白质合成等作用。     

肝动注阿霉素及其脂质体在体内的定量分析

进一步研究阿霉素及其脂质体在体内的行为,需要灵敏、精确的定量分析方法,本研究建立了适用于微量阿霉素及其脂质体以及其代谢产物Adriamycinol和Adriamycinone在动物组织、血浆及尿中的高效液相分析方法。     

肝动脉注射阿霉素温度敏感脂质体的靶行为和治疗应用的研究

Yatvin成功地用温度敏感脂质体进一步提高了脂质体在靶治疗中的中靶功能。本文还根据荷瘤肝脏的血流分布特性,将研制成功的阿霉素(adriamycin)温度敏感脂质体注入肝动脉,并与热疗相结合,对阿霉素温度敏感脂质体的体内行为和疗效进行研究,证明有提高抗肝癌疗效的可能。     

多糖多相脂质体的物理性质与稳定性研究

本文主要研究多糖多相脂质体的物理性质——多相脂质体加热灭菌前后的形状、结构、粒度分布变化以及对药物丝裂霉素的包封率和聚结稳定性。实验证明:多糖多相脂质体的热稳定性好。经100℃60 min灭菌可保持完整多相脂质体形态、均匀的粒径与稳定的包封率。用Coulter计数仪测定了贮存过程中聚结成人粒子的变化规律。测得其聚结活化能E=99.992 kJmol^-1,是比较稳定的多相脂质体。     

双多糖多相脂质体的研究——1.多糖中有效成分的选择和鉴定

用乙醇分级沉淀的方法将人参多糖和黄芪多糖分级、精制。研究了不同组分的纯度、分子量分布和单糖组成,并对其抗肿瘤作用进行了初步比较,为选择加入脂质体制剂中的多糖组分做了必要的实验准备。