脂质体阿霉素对淋巴瘤抑制模型的治疗效果

目的探讨脂质体阿霉素治疗淋巴瘤的效果和安全性。方法使用国产脂质体阿霉素在裸鼠淋巴瘤种植模型,分为生理盐水、单纯脂质体、普通阿霉素、脂质体阿霉素四组,比较了种植瘤的体积变化。结果脂质体阿霉素疗效优于传统药物,副作用明显少于普通阿霉素。结论淋巴瘤的治疗中脂质体阿霉素值得推广。     

脂质体载药提高阿霉素抗淋巴瘤活性的体内外研究

脂质体载药提高阿霉素抗淋巴瘤活性的体内外研究吴开达，范健，高雪芝，金宝翠（南京铁道医学院血液室，普外科．江苏２１０００９）阿霉素是一种抗瘤谱广、活力强．对多种肿瘤有效的强力抗癌剂．但由于其毒性较大而限制了临床广泛应用。脂质体是近年来发展较快的一种药物...     

脂质体载药降低阿霉素毒性的实验研究

阿霉素是一种抗瘤谱广、活性强的抗癌药物,已被广泛应用于消化道肿瘤的治疗.但由于严重的药物毒性,极大地限制了药物用量.本文通过制成脂质体阿霉素,与游离阿霉素比较其对小鼠的毒性,现报告如下.     

脂质体载药减少阿霉素心脏毒性的实验研究

目的：研究阿霉素（Ｆ－ＡＤＭ）和脂质体阿霉素（Ｌ－ＡＤＭ）对ＮＩＨ小鼠的心脏毒性。方法：采用卵磷脂、磷脂酸和胆固醇制备多层脂质体。实验动物分为阿霉素组和脂质体阿霉素组。其中１ｍｇ·ｋｇ－１对应剂量组观察药物分布；７．５、１５和２０ｍｇ·ｋｇ－１对应剂量组观察药物毒性。结果：用药后４和２４ｈ心肌内药物浓度分别为：阿霉素组８．６１、４．１１μｇ·ｇ－１，脂质体阿霉素组２．５３、０．９８μｇ·ｇ－１。阿霉素１５ｍｇ·ｋｇ－１组５例动物中Ⅲ级以上心肌损害４例，而脂质体阿霉素组无Ⅲ级以上损害。且心、肝、肾病理损害明显减轻。结论：含负电荷磷脂的脂质体载药后可明显减轻阿霉素对心肌的毒性损害。     

阿霉素脂质体的冻干工艺考察

目的:对阿霉素脂质体冻干工艺进行考察。方法:以外观、再分散性、粒径为指标,对冻干工艺中参数进行优化。结果:优化的冻干工艺为-75℃预冻24h,升温至-25℃保持16h,再升温至20℃持续8h,选择10%海藻糖作为阿霉素脂质体的冻干保护剂。结论:通过优化冻干工艺参数,所得的阿霉素脂质体冻干制品外观平整、质地疏松,加水后能迅速分散均匀。     

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     

吡喃阿霉素治疗恶性淋巴瘤的对比观察

应用吡喃阿霉素和阿霉素为主联合化疗分别治疗２５例恶性淋巴瘤，进行对比观察。两组病例治疗有效率均为８８．０％，无差异。药物毒副反应白细胞减少，血小板减少，恶心，呕吐两组间均无显著性差异。心脏，肝脏毒性及脱发发生率吡喃阿霉素组明显低于阿霉素组。     

新型阿霉素隐形阳离子脂质体的制备及体外细胞实验

目的制备阿霉素隐形阳离子脂质体(DOX-SCL),并与中性脂质体(DOX-SNL)比较在体外小鼠乳腺癌4T1细胞实验上的差异。方法采用薄膜超声法制备空白脂质体,硫酸铵梯度法包载盐酸阿霉素(DOX);引入赖氨酸-胆固醇酯(Chol-lys)制成阳离子脂质体(CL),同时引入聚乙二醇-胆固醇琥珀酸酯(CHEMS-PEG)制成隐形阳离子脂质体(SCL);采用凝胶柱-UV法测定包封率;采用MTT法测定细胞毒性及体外抗肿瘤活性;通过流式细胞试验考察4T1细胞对脂质体的摄取情况。结果 SCL粒径约为100 nm,Zeta电位约为15.2 mV,对DOX的包封率大于95%;CHEMS-PEG的引入可以有效地降低CL的细胞毒性;与DOX-SNL相比,4T1细胞对DOX-SCL的摄取有所增加,DOX-SCL对4T1细胞的抑制率也更高。结论 SCL作为新型药物载体,可有效地促进DOX在肿瘤细胞中的传递。     

MDP-阿霉素脂质体交联物治疗大鼠成骨肉瘤的药效学研究

目的：制备出MDP－阿霉素脂质体交联物（MDP－LADM），观察MDP－LADM治疗大鼠成骨肉瘤UMR106模型伯疗效，并与游离阿霉素（ADM）及阿霉素脂质体（LADM）作比较。方法：建立SD大鼠UMR106成骨肉瘤模型，将磷脂修饰后用1，4，－二异氰基甲苯酯（TDD与MDP交联，用改良的逆向蒸发将其制备成阿霉素脂质体－MDP交联物。将荷瘤大鼠随机分为五组，即生理盐水组，ADM组，游离ADM＋空白脂质体组，LADM组及MDP－LADM组，观察它们对大鼠的抑瘤作用。用高效液相色谱测定阿霉素在骨组织及其它器官中的含量。结果：MDP－阿霉素脂质体交联物对阿霉素包裹率为92．3％，MDP交联率为70．2％，对SD大鼠UMR106成骨肉瘤模型的抑瘤作用明显高于阿霉素（P＜0．01）和阿霉素脂质体（P＜0．05），治疗后大鼠生存期明显延长（P＜0．01），阿霉素在骨组织中的含量明显增加。结论：MDP－阿霉素脂质体交联物可明显提高阿霉素脂质体对骨肿瘤的治疗作用，降低其不良反应。     

N-三甲基壳聚糖包衣阿霉素脂质体与普通脂质体的抗肿瘤活性比较

目的:比较N-三甲基壳聚糖(TMC)包衣的盐酸阿霉素(ADM)脂质体与普通ADM脂质体的抗肿瘤活性。方法:采用硫酸铵梯度法制备ADM脂质体,以不同取代度的TMC进行包衣,采用动物移植性肿瘤实验法,用小鼠H22肝癌细胞接种于小鼠右侧腋下皮下形成实体瘤,考察TMC包衣ADM脂质体和普通脂质体给药后对实体瘤的瘤重抑制率。结果:TMC60、TMC40、TMC20包衣ADM脂质体对小鼠H22肝癌移植瘤的抑瘤率分别为64.3%,57.0%和54.8%,显著高于ADM脂质体组和游离ADM组(36.4%、42.7%)(P<0.05)。结论:TMC包衣ADM脂质体具有较好的抗肿瘤活性。     

脂质体阿霉素的制备及包封率测定方法的研究

目的：建立一种检测脂质体中阿霉素含量的方法。方法：对阿霉素溶液进行紫外可见光扫描,探求最佳波长。阿霉素脂质体溶液进行柱分离,找出脂质体和游离药物分离的最佳体积。结果：可以看出在２３２ｎｍ处阿霉素有最大吸收;脂质体和游离药物的最佳分离体积为２０ｍｌ。用紫外ＳｅｐｈａｄｅｘＧ５０法测定阿霉素脂质体的包封率为１０．３％±１．２％（ｎ＝４）,包封率测定回收实验表明,此法重复性好。结论：紫外ＳｅｐｈａｄｅｘＧ５０法测定阿霉素脂质体的包封率准确性高、重现性好、简便易行。     

阿霉素为主的化疗方案治疗非霍奇金淋巴瘤40例

目的：评价水剂阿霉素与粉剂阿霉素在临床疗效和安全性方面的差异。方法：在40例非霍奇金淋巴瘤（NHL）患者中，采用统一方案CHOP（环磷酰胺，阿霉素，长春新碱和泼尼松）。其中治疗组20例患者用水剂阿霉素，对照组20例患者用粉剂阿霉素。结果：治疗组有效率为85％，对照组有效率为80％，本研究表明二者在疗效及不良反应方面无差异。结论：水剂阿霉素在临床应用中是安全和有效的。     

芹菜素对阿霉素所致心脏毒性拮抗作用的研究

目的:研究芹菜素(API)对阿霉素所致中毒性心肌炎的拮抗作用。方法:120只健康昆明种小鼠随机分为6组:正常组、ADR模型组(27 mg·kg^-1)、芹菜素低剂量组(125 mg·kg^-1)、芹菜素中剂量组(250 mg·kg^-1)、芹菜素高剂量组(500 mg·kg^-1)、芹菜素高剂量对照组(500 mg·kg^-1)。观察各组小鼠的精神状态、进食、粪便及皮毛情况。ADR末次给药24 h后,检测小鼠全心质量指数(HW/BW),心肌组织匀浆后测定SOD活力和MDA含量变化,HE染色和透射电镜观察心肌形态学和超微结构改变。结果:ADR模型组小鼠精神状态差、体质量减轻、死亡率增加、HW/BW值降低、心肌组织SOD活力下降而MDA含量增加,与正常对照组小鼠有显著性差异(P<0.01)。光镜和电镜观察发现心肌损伤明显。芹菜素组可逆转上述表现,尤以芹菜素高剂量组作用明显,与ADR组比较有显著性差异。结论:芹菜素对阿霉素所致的小鼠心脏毒性具有拮抗作用。     

二氢杨梅素对小鼠移植性肉瘤S180化疗的增效减毒作用

目的:探讨二氢杨梅素(dihydromyricetin,DMY)联合阿霉素对小鼠移植性肉瘤的抑制效果。方法:建立小鼠移植性肉瘤模型,观察DMY和阿霉素处理后各组小鼠移植瘤大小和体重变化。结果:DMY治疗组具有抑制小鼠移植性肉瘤生长的作用,100 mg.kg-1的DMY治疗组的抑瘤率为48.6%(P<0.05);2 mg.kg-1的阿霉素治疗组的抑瘤率为64.4%,而2 mg.kg-1的阿霉素联合100 mg.kg-1的DMY治疗组的抑瘤率为75.4%(P<0.01)。DMY对阿霉素诱导小鼠血清中乳酸脱氢酶(LDH)和谷草转氨酶(AST)增加有明显的抑制作用(P<0.05)。结论:DMY和阿霉素对小鼠移植性肉瘤生长均有明显的抑制作用;DMY能增加阿霉素的抗肿瘤作用,且能降低阿霉素诱导的心肝毒性。     

Modeling cytoplasmic release of encapsulated oligonucleotides from cationic liposomes

Transfection activity of antisense oligodeoxynucleotides (ODN)-loaded cationic liposomes is mainly restricted by uptake and ODN release into cytoplasm, which is difficult to evaluate in cell culture studies. Well-designed models of cellular membranes, aim of the present study, might facilitate investigation of such processes. In this investigation, a phosphorothioate ODN was actively encapsulated in a DODAP-containing cationic liposome by ethanol injection with 73% efficiency. ODN release was determined by fluorescence dequenching of FITC-ODN upon incubation of liposomes with early endosomal (EE), late endosomal (LE) and plasma membranes (PM) models. LE provided the highest release (up to 76%) in a temperature-dependent manner. Release by EE (<16%), total PM (<11%) and PM external layer ( approximately 0) were not temperature sensitive. These differences are attributed to lipid charge, chain mobility, critical packing parameter and cholesterol content of the models. Intracellular distribution of FITC-ODN, determined by fluorescence microscopy and flowcytometry in the presence and absence of sodium azide, confirmed that liposomes were internalized mainly via endocytosis; hence inability of our PL models to simulate such active processes. Instead, release of ODN from endosomes into cytoplasm was pH-sensitive and in good agreement with model membrane studies in terms of amount and mechanism.     

Enhanced schistosomicidal efficacy of tartar emetic encapsulated in pegylated liposomes

The aim of the present study was to evaluate the ability of liposomes to improve the efficacy of tartar emetic (TA) against established Schistosoma mansoni infection. TA was used as a schistosomicidal drug model and both conventional liposomes (CL) and long-circulating pegylated liposomes (LCL) were evaluated. In the first experiment, TA, either free or encapsulated within CL or LCL, was given intraperitoneally (i.p.) as a single dose of 11 mg Sb/kg to mice experimentally infected with S. mansoni. Only the group treated with LCL showed a significant (55%) reduction in the worm burden, compared to the control groups (untreated or treated with empty LCL). In the second experiment, the efficacy of TA-containing LCL was evaluated at a higher dose (27 mg Sb/kg) by both subcutaneous (s.c.) and i.p. routes. Reduction levels of 67 and 82% were achieved by s.c. and i.p. routes, respectively. Strikingly, all mice survived to this high dose of antimony. This is in contrast with free TA that was lethal in 100% of mice at the same dose. The present work demonstrates that LCL reduce the acute toxicity of TA and effectively deliver this drug to S. mansoni during the late stages of parasite infection.