RMP-7及其衍生物对脂质体跨血脑屏障作用的影响

目的研究RMP-7及其衍生物对脂质体跨血脑屏障的促进作用。方法测定RMP-7与DSPE-PEG-NHS偶联的物质的量比；用血脑屏障的体外模型验证其生物活性；观察脑组织切片中伊文思蓝的荧光位置和强度，测定脑组织中伊文思蓝的浓度。结果RMP-7与DSPE-PEG-NHS偶联物质的量比为1∶1；RMP-7和DSPE-PEG-RMP-7能使过氧化合物酶跨血脑屏障体外模型的转运速率增加2～3倍，修饰脂质体后能使所包封的伊文思蓝在脑中的浓度增加。结论RMP-7与DSPE-PEG-RMP-7对脂质体跨血脑屏障均有促进作用，且后者效果更好。     

Pharmacokinetics of paclitaxel-containing liposomes in rats

In animal models, liposomal formulations of paclitaxel possess lower toxicity and equal antitumor efficacy compared with the clinical formulation, Taxol. The goal of this study was to determine the formulation dependence of paclitaxel pharmacokinetics in rats, in order to test the hypothesis that altered biodistribution of paclitaxel modifies the exposure of critical normal tissues. Paclitaxel was administered intravenously in either multilamellar (MLV) liposomes composed of phosphatidylglycerol/phosphatidylcholine (L-pac) or in the Cremophor EL/ethanol vehicle used for the Taxol formulation (Cre-pac). The dose was 40 mg/kg, and the infusion time was 8 to 9 minutes. Animals were killed at various times, and pharmacokinetic parameters were determined from the blood and tissue distribution of paclitaxel. The area under the concentration vs time curve (AUC) for blood was similar for the 2 formulations (L-pac: 38.1±3.32 μg-h/mL; Cre-pac: 34.5±0.994 μg-h/mL), however, the AUC for various tissues was formulation-dependent. For bone marrow, skin, kidney, brain, adipose, and muscle tissue, the AUC was statistically higher for Cre-pac. For spleen, a tissue of the reticuloendothelial system that is important in the clearance of liposomes, the AUC was statistically higher for L-pac. Apparent tissue partition coefficients (K_p) also were calculated. For bone marrow, a tissue in which paclitaxel exerts significant toxicity, K_p was 5-fold greater for paclitaxel in Cre-pac. The data are consistent with paclitaxel release from circulating liposomes, but with efflux delayed sufficiently to retain drug to a greater extent in the central (blood) compartment and reduce penetration into peripheral tissues. These effects may contribute to the reduced toxicity of liposomal formulations of paclitaxel.     

Skin oxygenation after topical application of liposome-entrapped benzyl nicotinate as measured by EPR oximetry in vivo: Influence of composition and size

New and improved drug delivery systems are the important subject of much scientific research. The development of formulations that increase skin oxygenation and of methods for measuring oxygen levels in skin are important for dealing with healing processes affected by the level of oxygen. We have use EPR oximetry in vivo to compare the influence of liposomal formulations of different size and composition with that of hydrogel with respect to the action of the entrapped benzyl nicotinate (BN). Following the topical application of BN onto the skin of mice, pO₂ increase was measured by low-frequency EPR as a function of time. The effect of BN was evaluated by 3 different parameters: lag-time, time needed for maximum pO₂ increase, and overall effectiveness expressed by the area under the response-time curve. An increase in skin oxygenation was observed after BN application. The results show that the effect of BN incorporated in liposomes is achieved more rapidly than the effect from hydrophilic gel. The composition of the liposomes significantly affects the time at which BN starts to act and, to a lesser extent, the maximum increase of pO₂ in skin and the effectiveness of BN action. However, the size of the liposomes influences both the effectiveness of BN action and the time at which BN starts to act. After repeated application of liposomes, the pO₂ baseline increased and the response of the skin tissue was faster. Our results demonstrate that EPR oximetry is a useful method for evaluating oxygen changes after drug application and for following the time course of their action.     

RMP-7对两性霉素B脂质体跨血脑屏障能力的药效学研究RMP-7对两性霉素B脂质体跨血脑屏障能力的药效学研究

目的研究两性霉素B脑靶向脂质体对小鼠脑膜炎的治疗作用。方法用薄膜超声法制备两性霉素B脂质体和两性霉素B脑靶向脂质体,测定其包封率和浓度;建立小鼠的脑膜炎模型,研究了两性霉素B脂质体的疗效。结果两性霉素B脂质体的包封率为(93.3±1.8)%;脑内注射白色念珠球菌2 h使小鼠形成脑膜炎模型;将两性霉素B制成脑靶向脂质体,能显著延长脑膜炎小鼠的生存期。结论与普通两性霉素B脂质体相比,两性霉素B脑靶向脂质体能显著提高对小鼠脑膜炎的治疗作用,使小鼠的存活期延长一倍。     

25例晚期及复发子宫内膜癌紫杉醇联合化疗分析

[目的]评价紫杉醇联合化疗治疗晚期、复发子宫内膜癌的近期疗效及毒副作用.[方法]25例Ⅲ、Ⅳ期或复发的子宫内膜癌行紫杉醇 卡铂(或顺铂)化疗,紫杉醇135mg/m2～150mg/m2,卡铂AUC 4～5,或顺铂70mg/m2.[结果]有可测肿瘤或CA125/CA199升高16例,共进行63个疗程化疗,完全缓解37.5%,部分缓解25.0%,总有效率62.5%.完全缓解者无进展期平均5.3个月.无肿瘤监测指标9例,进行29个疗程化疗,中数随诊11.5个月无复发.3、4级白细胞下降40.0%,3级血小板下降11.4%.[结论]紫杉醇 卡铂或顺铂联合化疗对晚期、复发的子宫内膜癌有较好疗效.     

紫杉醇与顺铂联合治疗晚期鼻咽癌50例分析

[目的]探讨紫杉醇与顺铂(TP)联合应用治疗复发和远处转移的晚期鼻咽癌疗效.[方法]用TP方案治疗晚期鼻咽癌病人50例.3周为1个疗程,2个疗程后评定疗效,有效者继续原方案治疗4个疗程.[结果]有效率62%,其中CR 12%,PR 50%;随访时间24个月(10个月～4年),中位生存期16.5个月(4～30个月).所有病例均出现脱发,Ⅰ～Ⅱ度骨髓抑制,消化道反应较重,其他不良反应轻微.[结论]TP方案对晚期鼻咽癌有较好的近期疗效,缓解期为6个月左右,多疗程治疗有利于改善预后.     

表柔比星加紫杉醇新辅助化疗方案治疗乳腺癌

目的:研究表柔比星加紫杉醇新辅助化疗方案治疗乳腺癌的近期疗效及毒副反应。方法:用TE方案(紫杉醇加表柔比星)对Ⅱ、Ⅲ期的20例乳腺癌进行新辅助化疗,3-4周为1个周期,患者完成2-4个周期后评价疗效;并以VE方案(长春瑞滨加表柔比星)作对照组进行比较,TE方案:表柔比星(EPI)60 mg/m2,第1天,静脉注射;紫杉醇(TAX)150mg/m2,第2天,静脉点滴;3周为1个周期。VE方案:EPI 60mg/m2,第1天,静脉注射;长春瑞滨(VNR)30mg/m2,第1、8天,静脉注射;4周为1个周期。结果:TE组有效率为80％,其中临床完全缓解(cCR)3例,部分缓解(PR)13例,无变化(NC)4例,病理完全缓解(pCR)2例;VE组有效率为80％,其中cCR 3例,PR 13例,NC 4例,pCR2例。两组均无进展(PD)者。进行4周期新辅助化疗患者有效率高于2周期患者。两组白细胞下降、胃肠道反应、面色潮红和静脉炎等毒副反应相似,VE组乏力、脱发、神经毒性程度比TE组显著(P<0.05),而在关节头痛方面TE组显著(P<0.05)。结论:两组新辅助化疗方案治疗乳腺癌近期有效率较高,疗效相当;VE组毒副反应较TE组高,但均可耐受。     

氟尿嘧啶/亚叶酸联合奥沙利铂或紫杉醇治疗晚期胃癌--临床随机对比研究

目的：比较氟尿嘧啶／亚叶酸(5-FU／FA)联合奥沙利铂与5-FU／FA联合紫杉醇治疗晚期胃癌的近期疗效和毒副反应。方法：40例进展期胃癌患者随机分成两组，5-FU／FA联合奥沙利铂组(A组)20例，70．0％为复治患者，5-FU／FA联合紫杉醇组(B组)20例，55．0％为复治患者，转移部位包括肝、淋巴结、腹腔、腹壁等。结果：两组患者各有20例可评价疗效，A组CR2例，PR7例，有效率(CR PR)45．0％，B组PR9例，有效率45．0％。A组有20例评价毒性反应，主要为骨髓抑制、外周神经毒性、消化道反应、肝功能损害；B组有20例可评价毒性反应，主要为骨髓抑制、肝功能损害。结论：5-FU／FA联合奥沙利铂与联合紫杉醇治疗晚期胃癌疗效相当．毒性反应可耐受。两者相比，联合奥沙利铂具有用药方便，严重的毒副反应少等优点。     

A phase II study of carboplatin and paclitaxel in esophageal cancer.

BACKGROUND: This study was conducted to evaluate the efficacy and toxicity of combination carboplatin and paclitaxel in patients with esophageal cancer. MATERIALS AND METHODS: Thirty-five patients were enrolled. Patients were treated with paclitaxel 200 mg/m(2) intravenously (i.v.) over 3 h and carboplatin i.v. at an AUC of 5 mg/h/ml. Thirty-three patients were assessable for toxicity and objective response. RESULTS: A total of 166 treatment courses were administered with a median of five courses per patient. The objective response rate was 43% [90% confidence interval (CI) 0.3-0.58] by the intention-to-treat analysis. The median response duration was 2.8 months (90% CI 2.1-5.4). The median survival time was 9 months (90% CI 7-13.8) and the 1-year survival rate was 43% (90% CI 0.29-0.57). The major grade 3-4 toxicity observed was neutropenia, occurring in 17 patients (52%). There were no treatment-related deaths. CONCLUSIONS: The combination of carboplatin and paclitaxel is an moderately active and tolerable regimen in advanced esophageal cancer.     

反应停、紫杉醇对Lewis肺癌小鼠的抑瘤作用

目的　研究反应停、小剂量紫杉醇对 L ewis肺癌小鼠皮下移植瘤和肺转移瘤的抑制作用 ,并探讨其与肿瘤细胞凋亡和细胞周期的关系。方法　 50只荷 L ewis肺癌小鼠随机分为四组 ,分别给予生理盐水、反应停、小剂量紫杉醇、反应停联合小剂量紫杉醇治疗 ,第 2 1天处死动物 ,称取鼠重、瘤重、肺重 ,计数肺转移结节数 ,免疫组化染色记数肿瘤组织微血管密度 ,流式细胞仪检测肿瘤细胞凋亡率及细胞周期。结果　反应停、小剂量紫杉醇单独及联合治疗组肿瘤重量与对照组间差异无显著性 (P>0 .0 5)。反应停、小剂量紫杉醇单独及联合治疗组肺重、肺转移结节数及肿瘤组织微血管密度均小于对照组 ,差异有显著性 (P<0 .0 5)。各治疗组肿瘤细胞凋亡率及 G1、S、G2 期肿瘤细胞百分数与对照组间差异无显著性 (P>0 .0 5)。结论　反应停、小剂量紫杉醇不能抑制 L ewis肺癌皮下移植瘤生长 ,但可抑制肿瘤肺转移 ,两药间无协同或拮抗作用。反应停、小剂量紫杉醇不诱导 L ewis肺癌细胞凋亡 ,不影响肿瘤细胞生长周期