紫杉醇脂质体经动脉介入治疗恶性肿瘤32例疗效观察

目的观察紫杉醇脂质体经动脉灌注介入治疗恶性肿瘤的临床疗效和药物不良反应，评价其疗效和用药安全性。方法对32例恶性肿瘤患者均经股动脉穿刺，插管至肿瘤的靶血管，通过导管局部灌注紫杉醇脂质体90mg；肺癌和盆腔恶性肿瘤再灌注顺铂60mg，肝癌和转移性肝癌再灌注5-氟尿嘧啶1000mg。此外有部分肝癌和转移性肝癌患者进行了栓塞治疗。结果32例恶性肿瘤患者经过动脉灌注紫杉醇脂质体介入治疗，总的临床疗效达到50．0％，并且药物不良反应较轻，患者住院时间短。结论应用紫杉醇脂质体经动脉灌注介入治疗恶性肿瘤具有近期疗效好，药物不良反应轻，耐受性好等优点，临床应用安全有效。     

荧光脂质体法研究芍药甘草汤对磷脂酶A2的抑制效应及其配伍作用

目的 采用荧光脂质体研究芍药甘草汤对磷脂酶A2(PLA2)的抑制效应及其配伍作用.方法 以磷脂酰胆碱和胆固醇等为主要材料,采用薄膜分散法-超声-膜挤出-葡聚糖凝胶柱色谱分离-冷冻干燥的联用技术制备包封羧基荧光素的脂质体;利用PLA2能水解磷脂破坏脂质体造成羧基荧光素渗漏的原理,将药物、PLA2和荧光脂质体共同温孵,检测从脂质体渗漏的羧基荧光索的荧光强度,该强度反映药物对PLA2的抑制强度.结果 芍药甘草汤、甘草、甘草酸和对照药氯丙嗪对PLA2活性均具有较强的抑制作用,白芍抑制作用较弱,而芍药苷几乎无抑制作用;芍药甘草汤复方对PLA2的抑制作用强于单味甘草和白芍.结论 芍药甘草汤对PLA2具有较强的抑制活性,白芍与甘草具有协同作用.     

干扰素α脂质体凝胶剂的透皮吸收作用研究

目的探讨基因重组人干扰素α-2b脂质体凝胶剂经家兔皮肤给药后的吸收作用。方法给家兔皮肤分别涂抹干扰素α-2b脂质体凝胶（试验组）和干扰素α-2b凝胶（对照组），用双抗体夹心酶联免疫吸附法（ELISA法）检测干扰素含量，测定给药后不同时间内血浆中干扰素含量及24h后皮肤层中的干扰素含量。结果与对照组比较，试验组干扰素在家兔皮肤层中有较多的滞留量（P〈0．01）；两组家兔不同时间血浆中干扰素的含量均极微少（P〉0．05）。结论脂质体作为干扰素皮肤局部给药的载体，能够提高干扰素在皮肤中的含量，但并不增加进入血液循环的干扰素量。     

环孢素长循环脂质体的制备、特征和药动学研究

 目的制备环孢素的长循环脂质体,改善环孢素的溶解度,替代临床现用制剂中所用的有毒致敏辅料,延长药物在体循环中的停留时间。方法采用改良的乙醇注入结合超声分散的方法制备环孢素长循环脂质体,蔗糖作为冻干保护剂冻干。同时采用葡聚糖凝胶柱、透析和超滤的方法分离游离药物和脂质体,以HPLC计算环孢素的包封率(EE)。以载药量、粒径等为指标,采用中心复合设计对处方进行优化,最优处方配比为卵磷脂、胆固醇、环孢素和单甲氧基聚乙二醇磷脂酰乙醇胺摩尔比为(95/40/4.5/5)。研究了大鼠体内的药动学,并与市售山地明注射剂作比较。结果优化条件下制备的长循环脂质体的体积平均粒径是(50.3±5.1)nm(n=6),采用超滤法测得的包封率为97%。体内药动学研究表明,与山地明相比,环孢素长循环脂质体的Vc减小30%(P<0.01),AUC增加30%(P<0.05),MRT延长8%(P<0.01),CLt减少59%(P<0.05)。结论本法制备的聚乙二醇修饰环孢素脂质体,粒径满意,包封率高,初步的体内外研究数据表明,具有一定的长循环作用,制备方法简单,重现性好。     

聚(2-乙基丙烯酸)脂肪酰胺衍生物构建的酸敏脂质体

本实验合成了系列聚(2-乙基丙烯酸)长链脂肪酰胺衍生物，并采用高分子插入法制备了聚(2-乙基丙烯酸)酸敏高分子脂质体。应用荧光指示剂、粒径仪、荧光显微镜及细胞实验，系统研究了高分子修饰和脂肪胺的链长对高分子衍生物嵌入脂质体的效率和质量的影响。结果表明，高分子插入法可以制备聚(2-乙基丙烯酸)酸敏高分子脂质体。(1) 高分子嵌入量与高分子脂肪胺的链长无关，但与高分子修饰度相关。(2) 高分子嵌入量与起始的高分子-脂质体比例成正比。(3) 在酸性条件下聚(2-乙基丙烯酸)脂质体可产生显著的脂质体融合及释药行为。(4) 聚(2-乙基丙烯酸)脂质体在细胞内呈现出良好的酸敏诱导释药特性。实验证明这种方法制备的脂质体具有良好的酸敏释药性能，并且制备方法简便，可控性好，实用性强。     

紫杉醇脂质体在家兔体内的药动学研究

目的建立家兔血浆中紫杉醇HPLC检测方法,研究紫杉醇脂质体在家兔体内的药动学规律。方法家兔血样采用叔丁基甲醚提取后在Hypersil C18柱上以甲醇∶水(65∶35)为流动相,检测波长为227 nm,地西泮为内标条件下进行检测。结果血药浓度在0.1~40.0 mg/L范围内线性关系良好(r=0.9997),提取回收率大于82.0%,日内、日间精密度分析RSD<6.0%。用本法对家兔耳缘静脉注射紫杉醇脂质体(12 mg/kg)后药动学进行研究,经DAS2.0软件拟合,脂质体制剂中紫杉醇血药浓度经时曲线符合二室模型,主要药动学参数如下:t1/2α为1.21±0.21 h,t1/2β为33.56±6.69 h,Vd为0.81±0.09 L,CL为0.04±0.01 L/h,AUC0-t为321.11±18.46 mg.h-1.L-1,AUC0→∞为722.20±170.36 mg.h-1.L-1,K10为0.04±0.01/h,K12为0.25±0.04/h,K21为0.32±0.06/h。结论本实验方法简便易行,结果可靠,可用于紫杉醇脂质体的药动学研究。     

脂质体介导的体内外细胞因子基因转移效果的初步研究

本研究用反相蒸发技术制备出包裹IL-2 DNA或IL-6 DNA的脂质体，将其与体外培养的靶细胞共育，或将其直接注射至小鼠腹腔内及荷瘤小鼠的瘤体内．研究其介导体内外基因转移的效果，结果表明我们研制的脂质体不但能将目的基因转移至体外培养的靶细胞中，并可通过腹腔内注射及瘤体内注射后，在腹腔内及肿瘤原位直接将IL-2和IL-6基因转移至腹腔细胞及肿瘤细胞中，稳定表达IL-2和IL-6。     

脂质体瘤苗特异性主动免疫的实验治疗

用同系肿瘤相关抗原脂质体瘤苗免疫ＩＣＲ小鼠后分别接种１×１０５肝癌Ｈ２２细胞或艾氏腹水瘤细胞。实验显示：未免疫的动物全部死亡，免疫动物部分（１０％～３０％）存活。死于肿瘤的动物其平均存活时间，免疫组要比对照组明显延长（Ｐ＜０．０１）。     

Phase II trial of pegylated-liposomal doxorubicin (Doxil) in renal cell cancer

Twelve patients with refractory renal cell cancer weretreated on a phase II study of pegylated-liposomaldoxorubicin (Doxil). The initial dose per course was55 mg/m² every four weeks with dose modification based onmucositis and hand-foot syndrome (the main limitingtoxicities). Toxicities were mild and similar to previousreports but dose reduction per the study protocol, which wasdesigned to control the skin and mucosal toxicities, wascommon. No definite cardiac toxicity was observed. Noobjective responses were observed in 11 evaluable patients. This study did not demonstrate activity ofpegylated-liposomal doxorubicin in renal cell cancer,although it can be given with mild toxicity.     

Targeting Efficiency of Galactosylated Liposomes to Hepatocytes in Vivo: Effect of Lipid Composition

Purpose. To investigate the effects of the lipid composition of galactosylated liposomes on their targeted delivery to hepatocytes. Methods. Several types of liposomes with a particle size of about 90 nm were prepared using distearoyl-L-phosphatidylcholine (DSPC), cholesterol (Chol) and cholesten-5-yloxy-N-(4-((1-imino-2-D-thiogalactosylethyl)amino)butyl)formamide (Gal-C4-Chol), and labeled with [³H]cholesterol hexadecyl ether. Their tissue disposition was investigated in mice following intravenous injection. The binding and internalization characteristics were also studied in HepG2 cells. Results. Compared with [³H]DSPC/Chol (60:40) liposomes, [³H]D-SPC/Chol/Gal-C4-Chol (60:35:5) liposomes exhibit extensive hepatic uptake. Separation of the liver cells showed that galactosylated liposomes are preferentially taken up by hepatocytes, whereas those lacking Gal-C4-Chol distribute equally to hepatocytes and nonparenchymal cells (NPC). Increasing the molar ratio of DSPC to 90% resulted in enhanced NPC uptake of both liposomes, suggesting their uptake via a mechanism other than asialoglycoprotein receptors. DSPC/Chol/Gal-C4-Chol (60:35:5) and DSPC/Chol/Gal-C4-Chol (90:5:5) liposomes exhibited similar binding to the surface of HepG2 cells, but the former were taken up faster by the cells. Conclusions. The recognition of galactosylated liposomes by the asialoglycoprotein receptors is dependent on the lipid composition. Cholesterol-rich galactosylated liposomes, exhibiting less non-specific interaction and greater receptor-mediated uptake, are better for targeting drugs to hepatocytes in vivo.