总姜黄素脂质体的包封率和体外释药测定

目的:研究总姜黄素脂质体的包封率测定方法,初步考察其体外释放规律。方法:用乙醇注入法制备了总姜黄素脂质体,葡聚糖凝胶 G-50柱分离方法测定脂质体的包封率,并用溶出度第三法考察脂质体的体外释放过程。分析柱为岛津 C_(18)色谱柱(150 mm×4.6 mm,5μm),乙腈-水-冰醋酸(45:55:2)为流动相,流速1mL·min~(-1),检测波长430nm。结果:总姜黄素脂质体的平均包封率为64.4%,体外释放符合一室模型。结论:该方法简便、易操作,可作为总姜黄素脂质体包封率和体外释药的研究。     

藻酸双酯钠脂质体的制备及粒度分布的测定

目的制备藻酸双酯钠脂质体并对其聚结稳定性进行评价。方法采用蛋黄卵磷脂为包封材料,逆向蒸发法制备藻酸双酯钠脂质体,将藻酸双酯钠脂质体与空白脂质体对照,分别测定了它们经37℃,40h温育前后的粒度分布,计算平均粒径。结果在n(PC)∶n(CHOL)=1∶1的条件下,藻酸双酯钠脂质体的平均粒径为4.24μm,温育后,藻酸双酯钠脂质体的平均粒径只增加了0.26μm,而空白脂质体的平均粒径增加了1.35μm。结论藻酸双酯钠载于脂质体上,提高了脂质体的聚结稳定性。     

温敏凝胶释药模式及机制研究进展

温敏凝胶因具临界相转变温度而被作为能达到定点、定时、定量释药目的药物控释体系的载体之一成为近年来研究的热点。随着温敏凝胶研究和应用的不断深入,其释药模式及机制被不断提出和发现,不同释药特征的释药模型也相继建立。温敏凝胶释药模型、模式及机制的研究透彻将使温敏凝胶在医药、生物等领域得到更好的应用。     

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。     

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.     

Intrathecal administration of liposomal neostigmine prolongs analgesia in mice

BACKGROUND: There is substantial evidence that cholinomimetic drugs increase pain threshold. However, the profound side effects of these agents have limited their clinical use either as analgesics or as analgesic adjuncts. A delivery system that would assure a slow and sustained drug release may be of value in ameliorating the problem of untoward effects. METHODS: The acetylcholinesterase inhibitor neostigmine was encapsulated into multilamellar lipid vesicles composed of phosphocholine and cholesterol. Three doses of plain or liposomal neostigmine were administered by the intrathecal route to mice (n=8-10/group), and analgesic duration was quantified by tail flick test. The doses were chosen based on preliminary experiments, which showed the maximum tolerated intrathecal doses of plain and liposomal neostigmine formulation were 0.625 microg and 80 microg, respectively. Two other doses for each formulation were then derived by 1:1 serial dilutions. Results were compared using survival analysis. RESULTS: The median antinociceptive duration for plain neostigmine was 0.33, 0.99 and 1.0 h for the 0.115, 0.312 and 0.625 microg doses, respectively. For the liposomal formulation, the median antinociceptive duration was 1.0, 1.5 and 6.0 h for the 20, 40 and 80 microg doses, respectively. CONCLUSIONS: Liposomal neostigmine provides prolonged spinal antinociception, and permits the safe administration of a relatively large dose, because drug is gradually released from the liposomal depot. This technology holds promise for the development of a clinically useful neostigmine formulation to provide spinal analgesia.