载紫杉醇聚己内酯-聚乙二醇-聚己内酯胶束的制备及药代动力学研究

目的制备新型可注射用载紫杉醇聚己内酯-聚乙二醇-聚己内酯(PCL-PEG-PCL)胶束,并评价和比较其与市售紫杉醇注射液在大鼠体内的药代动力学性质。方法以PCL-PEG-PCL为载体材料,通过薄膜-水化-超声法制备出载紫杉醇PCL-PEG-PCL胶束,并对其进行表征。以市售紫杉醇注射液为对照,采用SD大鼠尾静脉注射后观察载紫杉醇PCLPEG-PCL胶束的体内药代动力学,并用DAS 2.0药代动力学数据软件计算相关参数。结果载紫杉醇PCL-PEG-PCL胶束呈大小均匀的球形,具有明显的核壳结构;平均粒径为93 nm,多分散系数为0.19;载药量为28.98%,药物包封率为94.36%。体外释放研究表明,载紫杉醇PCL-PEG-PCL胶束具有缓释效果。药代动力学研究表明,两种制剂均符合二房室模型,市售紫杉醇注射液和紫杉醇聚合物胶束消除半衰期(t1/2β)分别为(1.96±0.27)h和(12.65±1.77)h,平均滞留时间(MRT)分别为(0.93±0.19)h和(11.18±1.41)h,体内总清除率(CL)分别为(0.44±0.05)L·kg/h和(0.10±0.01)L·kg/h,药-时曲线下面积(AUC0-∞)分别为(17.15±2.35)mg·h/L和(73.82±10.38)mg·h/L。结论成功制备了新型可注射用载紫杉醇PCL-PEG-PCL胶束,药代动力学研究表明,所研制的载紫杉醇PCL-PEG-PCL胶束明显延长紫杉醇在血液中的循环时间及消除半衰期,显著提高生物利用度,是一种有潜力的紫杉醇缓控释新剂型。     

紫杉醇聚合物胶束及其抗肿瘤活性研究

目的 以聚己内酯-聚乙二醇-聚己内酯（PCL-PEG-PCL）为载体材料,制备载紫杉醇聚合物胶束,并评价其对EMT-6乳腺癌的抗肿瘤效果.方法 采用薄膜-超声法制备载紫杉醇聚合物胶束并对其进行表征;采用差示扫描热分析法（DSC）分析紫杉醇在载药聚合物胶束中的分散状态;采用MTT法研究紫杉醇聚合物胶束对EMT-6乳腺癌细胞的细胞毒性;建立荷EMT-6乳腺癌小鼠模型,以市售紫杉醇注射液为对照,研究紫杉醇聚合物胶束的体内抗肿瘤活性.结果 紫杉醇聚合物胶束为表面粗糙的球形,具有明显核壳结构,平均粒径为93nm;DSC研究结果表明,将紫杉醇制成缓释纳米粒后其结晶状态发生了变化,以无定型状态存在于聚合物胶束中;MTT研究表明,在相同紫杉醇含量下,紫杉醇聚合物胶束的细胞毒性低于市售紫杉醇／聚氧乙烯蓖麻油注射剂;体内抗肿瘤活性研究表明,紫杉醇聚合物胶束对小鼠EMT-6乳腺癌具有明显抑制作用,相同给药剂量下其抑瘤效果优于紫杉醇注射剂（肿瘤抑制率：85.79％ vs 63.37％,P＜0.05）.结论 制备的载紫杉醇聚合物胶束高效低毒,是一种有潜力的可用于肿瘤治疗的纳米载药体系.     

紫杉醇聚己内酯／泊洛沙姆188载药纳米粒及其抗肿瘤活性

目的利用聚己内酯（PCL）与亲水性添加剂泊洛沙姆188（F68）共混物作为载体材料与抗癌药物紫杉醇组成纳米粒缓释载药系统,并评价其在裸鼠人乳腺癌B37实体瘤模型中的抗肿瘤效果。方法采用超声乳化／溶剂挥发法制备紫杉醇PCL/F68载药纳米粒：对紫杉醇PCI／F68载药纳米粒进行表征及高压液相色谱法（HPLC）测定包封率和体外释放度：利用差示扫描热分析（DSC）法分析紫杉醇在PCL／F68载药纳米粒中的分散状态;评价紫杉醇PCL／F68载药纳米粒在裸鼠人乳腺癌B37实体瘤模型中的抗肿瘤活性．结果紫杉醇PCL/F68载药纳米粒呈现规整的球形：平均粒径为150．50nm（标准差25．41nm）．多分散系数为O．18。紫杉醇PCI仃68纳米粒的载药量为18％,药物包封率为84-36％。紫杉醇PCIJF68载药纳米粒体外药物释放研究表明在50d的释放周期内累计释放量约为49％,接近零级释放（R=0．998）。体内抗肿瘤活性实验研究表明．紫杉醇PCL/F68载药纳米粒对裸鼠人乳腺癌B37实体瘤生长具有明显抑制作用。结论肿瘤局部注射紫杉醇PCL/F68载药纳米粒能够有效地抑制肿瘤的生长,     

紫杉醇聚己内酯／泊洛沙姆188共混载药微球及其抗肿瘤活性

目的本研究首次尝试利用聚己内酯（PCL）与亲水性添加剂泊洛沙姆188（Pluronic F68,F68）共混物作为载体材料与抗癌药物紫杉醇组成微球缓释载药系统。方法采用乳化,溶剂挥发法制备紫杉醇PCL/F68共混微球;考察紫杉醇PCL／F68共混微球的表面形态、平均粒径、包埋率及体外释放性能：利用DSC法分析紫杉醇在PCL／F68共混徽球中的分散状态;考察紫杉醇PCL/F68共混微球在小鼠肝癌H22腹水瘤模型中的抗肿瘤活性。结果表明载体材料中的亲水性添加剂F68可在微球表面形成孔状结构,F68的加入提高了紫杉醇从PCL／F68共混载药微球的释放并获得了接近恒定的释放性能;在小鼠肝癌H22腹水瘤模型中。紫杉醇PCL／F68共混载药微球对肿瘤生长具有抑制作用,荷瘤小鼠生存期明显延长。结论以PCL/F68共混物为载体制备的紫杉醇控释微球具有较高的释放能力和明显的控释效果．     

关节腔注射用甲氨蝶呤温敏性缓释凝胶的制备及性能考察

目的利用聚己内酯-聚乙二醇-聚己内酯（PCL-PEG-PCL）两亲性聚合物温敏凝胶作为载体材料,构建抗类风湿性关节炎药物甲氨蝶呤关节腔注射用给药体系。方法采用开环聚合法,以辛酸亚锡为催化剂、PEG1500为引发剂,与己内酯单体开环聚合得到PCL-PEG-PCL两亲性嵌段共聚物;对得到的PCL-PEG-PCL嵌段共聚物的组成结构及相对分子质量进行表征;采用翻转试管法测定PCL-PEG-PCL聚合物的溶胶-凝胶相转变温度,绘制溶胶-凝胶相转变曲线;评价甲氨蝶呤PCL-PEG-PCL温敏凝胶载药体系的缓释性能;考察PCL-PEG-PCL温敏凝胶关节腔注射后在大鼠体内的生物相容性。结果 PCL-PEG-PCL两亲性嵌段共聚物水溶液具有温敏性溶胶-凝胶相转变能力,其溶胶-凝胶相转变温度介于室温与体温之间。甲氨蝶呤PCL-PEG-PCL温敏凝胶的体外释放研究表明PCL-PEG-PCL温敏凝胶对甲氨蝶呤具有较好的缓释能力,提高载药量和温敏凝胶浓度将减缓甲氨蝶呤从PCL-PEG-PCL温敏凝胶的释放。大鼠滑膜苏木精-伊红染色结果显示,关节腔注射PCL-PEG-PCL温敏凝胶未引起炎症反应发生。结论 PCL-PEG-PCL温敏凝胶作为关节腔局部注射用载药体系具有较好的药物缓释性能和生物相容性。     

聚乙二醇-b-聚己内酯/聚己内酯单分散电喷微球的制备与亲水性研究

用静电喷雾法制备单分散性良好、亲水性的聚乙二醇-b-聚己内酯/聚己内酯(PEG-b-PCL/PCL)电喷微球。将聚乙二醇-b-聚己内酯(PEG-b-PCL)、聚己内酯(PCL)与氯仿混合磁力搅拌3 h后,采用静电喷雾的方法,以双亲(PEG-b-PCL)含量、流速、电压为变量,研究微球形态大小、粒径分布的变化,并研究微球亲水性随双亲含量的变化程度及微球在水中的分散性。双亲含10%～20%、流速1 mL/h、电压10 kV时能得到成球性佳、粒径5～6 μm的单分散性良好的微球,粒径的变异系数为15%～21%;双亲含量增至30%,微球之间由较多的纤维连接;双亲含量由0增至20%时,接触角由126.2°±4.8° 降至29.9°±4.9°,差异具有统计学意义(P<0.05),通过改变双亲含量能有效改善微球的亲水性,同时,加入10%～20%双亲的微球在水中分散性佳,能形成均匀的混悬液。PEG-b-PCL/ PCL能得到单分散、亲水性佳的微球,为进一步制备载药微球提供条件。     

聚己内酯-吐温80共聚物纳米粒在神经胶质瘤化疗中的应用

目的 研究新型载多西紫杉醇聚己内酯-吐温80共聚物(PCL-Tween 80)纳米粒在神经胶质瘤化疗中的应用.方法 以PCL-Tween 80和聚己内酯为材料,利用改良的溶剂萃取/挥发方法制备载多西紫杉醇纳米粒并进行性质表征.利用激光共聚焦显微镜观察纳米粒的细胞摄取情况,并利用噻唑蓝(MTT)法测定纳米粒对C6细胞的细胞毒作用.结果 载药纳米粒呈球形,粒径约为200 nm.PCL-Tween 80纳米粒的载药量为10%,28 d内可以释放包裹药物的34.90%.与同浓度的泰素帝(Taxotere(R))比较,载多西紫杉醇PCL-Tween 80纳米粒对C6细胞的细胞毒性作用更强.结论 载多西紫杉醇PCL-Tween 80纳米粒用于神经胶质瘤的化疗极具应用前景.     

脂肪干细胞携载汉黄芩苷聚己内酯-聚乙二醇胶束的制备

背景:汉黄芩苷已被证明有抗炎、神经保护等多种药理活性作用,但其半衰期短、难溶于水,有机溶剂溶解后不良反应大.研究发现,聚己内酯-聚乙二醇能够结合高度疏水的药物,解决药物难溶问题且可以达到缓释的效果,但无法精确靶向到达损伤部位,制成胶束后因其尺寸小,可以穿透细胞膜.目的:制备汉黄芩苷聚己内酯-聚乙二醇胶束以及脂肪干细胞携...     

新型两亲性超枝状大分子聚己内酯／聚缩水甘油醚纳米粒子实验研究

目的选择合适实验条件将两亲性超枝状大分子聚己内酯／聚缩水甘油醚制备成纳米粒子,以进一步应用于靶向药物传递载体。方法称取聚己内酯／聚缩水甘油醚（通过H^1NMR和GPC定性）30mg,溶于3mL丙酮和2mL乙醇混合溶剂中,在搅拌速度为250r／min的条件下。将上述溶液按250uL·min^-1速度注入30mL的蒸馏水中,搅拌过夜,减压挥发除掉溶剂,冷冻干燥得到纳米粒子。结果通过透射电镜观察,所得纳米粒子为球形,形状均匀,粒径约在50—100nm之间。结论本研究通过实验,首先合成分子量2×10^4U左右的聚己内酯／聚缩水甘油醚聚合物,通过×选择合适的溶剂。得到聚己内酯／聚缩水甘油醚纳米粒子。该方法操作简易,环境友好,易于后处理,所得纳米粒子大小均匀,通过后修饰,这种纳米粒子将有望被应用于体内靶向传递。     

医用聚己内酯埋植剂体内降解的研究

目的 对医用聚己内酯埋植剂材料合成及体内降解进行研究,了解埋植剂材料的性能. 方法 Pluronic F68经乙酰封端处理后与己内酯单体（CL）混合,加入催化剂于N2保护的聚合釜中,在140 ℃～170 ℃条件下聚合48 h,用挤出机制成管材.研究致孔剂的工艺、微孔的形成.用核磁共振和扫描电镜等方法观察聚己内酯埋植剂材料的结构.用氚标记的低相对分子量的聚己内酯胶囊植入大鼠皮下,测定其体内降解、吸收和排泄. 结果 含有F68的医用聚己内酯埋植剂材料（PCL/F68）在亲水介质中F68很快溶出,可形成多微孔结构.该材料起始相对分子量为66 000时,在体内可完整存在2年,2年后降解为低相对分子量碎片,可被机体吸收、排泄,不在体内积蓄. 结论 聚己内酯/F68埋植剂材料在体内可降解并主要通过粪便排出体外,不在体内积蓄,脏器中放射性极少.     

Multifunctional Pluronic P123/F127 mixed polymeric micelles loaded with paclitaxel for the treatment of multidrug resistant tumors

The aim of this study was to exploit the possibility of combination of active targeting function of folic acid by folate receptor-mediated endocytosis and overcoming multidrug resistance (MDR) by Pluronic block copolymers to promote drug delivery to MDR tumor following intravenous administration with paclitaxel (PTX) as model drug. Folic acid functionalized Pluronic P123/F127 mixed micelles encapsulating PTX (FPF-PTX) was firstly developed and tested in vitro and in vivo, while PTX-loaded Pluronic P123/F127 mixed micelles (PF-PTX) and Taxol were used as control. FPF-PTX was about 20 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake of FPF-PTX was found to be higher than that of PF-PTX due to the folate receptor-mediated endocytosis effect. In vitro cytotoxicity, cell apoptosis and cell cycle arrest studies also revealed that FPF-PTX was more potent than those of PF-PTX and Taxol. In vivo pharmacokinetic study in rats showed that the polymeric micelles significantly enhanced the bioavailability of PTX (～3 fold) than Taxol. Moreover, in BALB/c mice bearing KBv MDR tumor xenografts, stronger antitumor efficacy was shown in FPF-PTX group, with good correlation between in vitro and in vivo. In conclusion, folate-conjugated Pluronic micelles could be a potential vehicle for delivering hydrophobic chemotherapeutic drugs to MDR tumors.     

金纳多对脑梗死患者血液流变学及血管活性物质水平的影响

目的：探讨金纳多对脑梗死患者血液流变学及血管活性物质水平的影响。方法：选取2012年2月到2013年2月我院收治的脑梗死患者74例。根据随机数表法分为实验组和对照组,分别采用金纳多治疗和常规治疗。比较两组患者的临床疗效、血浆粘度、纤维蛋白原、血浆比粘度、全血还原比粘度、血细胞比容及ET、TXB2、PGF1α、CGRP水平。结果：实验组总有效率（89.2%）与对照组（67.6%）之间有明显差异,具有统计学意义（P〈0.05）。疗程结束后,实验组血浆粘度为（1.82±0.21）mpa？s,纤维蛋白原为（2.98±0.59）g/L,血浆比粘度为（1.49±0.15）,全血还原比粘度（7.38±1.79）,血细胞比容为（0.40±0.07）;对照组血浆粘度为（2.13±0.24）mpa？s,纤维蛋白原为（4.02±0.70）g/L,血浆比粘度为（1.63±0.19）,全血还原比粘度（7.12±1.63）,血细胞比容为（0.45±0.06）。两组患者的血液流变学指标与同组治疗前相比均有明显改善,且实验组改善情况更佳。以上差异均具有统计学意义（P〈0.05）。治疗后,实验组的ET为（55.61±18.32）ng/L,TXB2为（65.21±22.03）ng/L,PGF1α为（74.81±20.93）ng/L,CGRP为（50.09±14.27）ng/L;对照组的ET为（60.01±20.33）ng/L,TXB2为（7 2.1 9±2 3.6 7）ng/L,P G F 1α为（5 6.7 6±1 9.2 1）ng/L,CG R P为（2 3.0 8±1 3.7 6）ng/L。实验组的ET、TXB2、PGF1α、CGRP,对照组的ET、TXB2与同组治疗前比较均有明显改善,且实验组改善情况更佳,以上差异均具有统计学意义（P〈0.05）。结论：金纳多能够有效治疗脑梗死,改善患者血液流变学指标及血管活性物质水平,具有重要的临床价值。     

妊娠期糖尿病患者血清孤独G蛋白偶联受体配体和视黄酸受体反应蛋白2水平及其与胰岛素抵抗的关系

目的探讨妊娠期糖尿病(GDM)患者血清孤独G蛋白偶联受体(apelin)和视黄酸受体反应蛋白2(chemerin)水平及其与胰岛素抵抗的关系。方法选择2009年3月至2011年12月于泰安市中心医院门诊做产前检查的孕妇70名,其中糖耐量正常组(NGT)孕妇30名,妊娠期糖尿病组(GDM)孕妇40名。计算每个个体体重指数(BMI),以及胰岛素抵抗指数(HOMA-IR),测定空腹以及糖负荷后2h血清apelin、chemerin水平,空腹血清胰岛素(FINS)以及糖负荷2h后血清胰岛素(2h PINS)。结果 GDM组与NGT组相比较,体重指数差异有统计学意义(28.92±2.25kg/m2vs 23.83±1.46 kg/m2,P<0.05),并且空腹胰岛素[(19.08土3.65μIU/L vs 14.16±2.42μIU/L),P<0.05]、糖负荷2h后胰岛素[(45.14±30.56μIU/L vs36.52±21.23μIU/L),P<0.05]以及胰岛素抵抗指数差异也有统计学意义(3.98±0.76,2.85±0.48,P<0.05);与NGT组比较,GDM组空腹(468.34±31.25 pg/mL vs 392.74±17.35pg/mL)以及糖负荷2h后(575.61±40.48 pg/mL vs 452.64±21.91 pg/mL)血清apelin差异有统计学意义(均P<0.05),与NGT组比较,GDM组空腹(72.26±16.63μg/L vs 60.81±17.27μg/L)以及糖负荷2h后(75.87±22.14μg/L vs 65.86±20.22μg/L)血清chemerin差异有统计学意义(均P<0.05)。同时发现apelin与chemerin水平呈正相关(r=0.45,P<0.05),血清apelin、chemerin与BMI呈正相关(r=0.47,P<0.05;r=0.68,P<0.01),与FINS呈正相关(r=0.36,P<0.05,r=0.26,P<0.05),与2h PINS呈正相关(r=0.28,P>0.05;r=0.22,P<0.05),与HOMA-IR呈正相关(r=0.45,P<0.05;r=0.49,P<0.05)。结论妊娠期糖尿病患者血清apelin、chemerin水平与胰岛素抵抗密切相关,apelin、chemerin可能参与了妊娠期糖尿病患者代谢的改变。     

Pharmacokinetics, biodistribution, efficacy and safety of N-octyl-O-sulfate chitosan micelles loaded with paclitaxel

Paclitaxel (Taxol), PTX) is a promising anti-cancer drug and has been successfully used to treat a wide variety of cancers. Unfortunately, serious clinical side effects are associated with it, which are caused by PTX itself and non-aqueous vehicle containing Cremophor EL. Development of new formulation of PTX with better efficacy and fewer side effects is extremely urgent. In the present study, a N-octyl-O-sulfate chitosan (NOSC) micelle was developed and used as the delivery system for PTX. The pharmacokinetics, biodistribution, efficacy and safety of PTX-loaded NOSC micelles (PTX-M) were evaluated. The results showed that NOSC micelles had high drug loading capacity (69.9%) and entrapment efficiency (97.26%). The plasma AUC of PTX-M was 3.6-fold lower than that of Taxol; but the V(d) and CL of PTX-M were increased by 5.7 and 3.5-fold, respectively. Biodistribution study indicated that most of the PTX were distributed in liver, kidney, spleen, and lung and the longest retention effect was observed in the lung. Drug safety assessment studies including acute toxicity, hemolysis test, intravenous stimulation and injection anaphylaxis revealed that the PTX-M was safe for intravenous injection. Furthermore, the comparable antitumor efficacy of PTX-M and Taxol was observed at the same dose of 10 mg/kg in in vivo antitumor mice models inoculated with sarcoma180, enrich solid carcinoma (EC), hepatoma solidity (Heps), Lewis lung cancer cells and A-549 human lung cancer cells. These results clearly showed that PTX-M had the similar antitumor efficacy as Taxol, but significantly reduced the toxicity and improved the bioavailability of PTX.     

视频脑电监测下注射贝美格定位致痫灶的研究

目的：对连续24h监测无发作的顽固性癫痫患者进行贝美格静脉注射诱发痫性发作．辅助定位致痴灶。方法：在视频头皮或深部电极脑电图描记监测下,对需手术治疗的25例顽固性癫痼患者,以25mg/min的速度静脉匀违注射贝美格。最大剂量为150mg,对有发作的患者根据症状学和脑电图发作波形确定致痫灶。结果：30例患者中出现临床发作25例（83％）,其中21例（84％）能通过脑电图大致判定致痫灶,与日常发作组对比差异无统计学意义（P〉0．05）,2例（8％）能大致判断癫痫起源侧别,1例无法判定致痫灶,1例（4％）出现新症状,其深部电极脑电图显示贝美格诱发的致痫灶与自然发作脑电起源不符。临床发作者注射贝美格剂量为（108．0±30．8）mg,发作后均静脉沣射0．2g苯巴比妥,发作停止时间为（3．0±1．0）min,发作前未见诱发出新位置的痢样放电。结论：贝美格诱发试验在诱发痫性发作对致痫灶定位有辅助作用,其原理可能与其使致痫灶的痫样放电被激活或使之更加活跃有关。     

Poly(caprolactone)-modified Pluronic P105 micelles for reversal of paclitaxcel-resistance in SKOV-3 tumors

Three poly(caprolactone)-modified Pluronic P105 polymers (P105/PCLs) were synthesized using commercially available ε-caprolactone monomers and Pluronic P105 copolymers. The chemical structures, compositions and molecular weights of the P105/PCLs were confirmed by FT-IR, (1)H NMR and GPC measurements. Three paclitaxel (PTX)-loaded P105/PCL polymeric micelles were then prepared, and they showed average diameters in the range of 30-150 nm, drug-loading coefficients of 0.15%-5.43%, and encapsulation ratios of 2.1%-76.53%. The in vitro cytotoxicity assay demonstrated that three PTX-loaded P105/PCL micelles were able to sensitize the resistant SKOV-3/PTX tumor cells. The PTX-loaded P105/PCL(50) micelle was then selected for an in vivo antitumor efficacy study. The tumor volumes in nude mice bearing s.c. resistant SKOV-3/PTX carcinoma treated with this micellar PTX were significantly less than the control group treated with Taxol. It was demonstrated that three PCL-modified P105 monomers and micelles inhibited P-gP efflux activity in the resistant SKOV-3/PTX cells via at least three intracellular events: 1) inhibition of ATPase of P-gP, 2) decrease of membrane microviscosity and 3) a loss of mitochondrial membrane potential and subsequent decrease of ATP levels at the concentration of monomers (0.001%) and/or micelles (0.01-1.0%). Considering other favorable characteristics, such as sustained PTX release in vitro, long-circulating time in vivo and increased PTX concentration in the tissues of ovaries and uterus in mice, the PCL-modified Pluronic P105 polymeric micelle system could have important clinical implications for delivery of paclitaxel and treatment of the resistant ovarian tumors.     

高龄患者卒中相关性肺炎的营养治疗疗效观察

目的研究高龄患者卒中相关性肺炎肠内外营养治疗的效果。方法将50例高龄患者卒中相关性肺炎随机分为肠内营养（EN）组和肠外营养（PN）组,每组25例。EN组采用鼻饲肠内营养液,PN组为静脉注入营养液,在摄入同等热量和氮量的条件下比较营养支持后两组NIHSS评分、血红蛋白、帆清总蛋白、白蛋白含量。结果治疗21d后,EN组血红蛋白（111±10．9）g／L、血清总蛋白（67．3±7．0）g/L、白蛋白（36．3±3．2）g/L,明显高于PN组（P〈0．05）,EN组NIHSS评分（9．3±1．4）明显低于PN组（11．3±1．4）（P〈0．05）,且并发症明显低于PN组。结论高龄患者卒中相关性肺炎早期给予肠内营养,可明显改善患者营养状态,促进神经功能的恢复,并且并发症少。     

颅脑损伤患者血浆NPY及CGRP检测的临床意义

目的探讨血浆神经肽Y（NPY）和降钙素基因相关肽（CGRP）水平在不同程度颅脑外伤患者中的临床意义。方法采用放射免疫方法（RIA）对91例依据GCS评分法分为轻度、中度和重度的颅脑损伤患者及35例正常对照组的NPY、CGRP和ET-1水平进行检测。结果轻、中、重三组颅脑损伤患者血浆NPY水平分别为（119.6±20.3）ng/L、（127.8±25.5）ng/L和（146.2±30.5）ng/L,显著高于正常对照组（65.2±13.2）ng/L,差异有统计学意义（P〈0.01）。轻、中度患者血浆CGRP含量分别为（54.3±5.6）ng/L、（57.5±7.4）ng/L,显著高于正常对照组（41.8±6.8）ng/L,差异有统计学意义（P〈0.01）;而重度患者组的CGRP水平（44.6±5.3）ng/L与对照组（41.8±6.8）ng/L间差异无统计学意义（P〉0.05）。结论血浆NPY及CGRP水平与不同程度颅脑损伤患者的病情密切相关,并对患者预后的判定具有一定的临床参考价值。     

Targeted and intracellular delivery of paclitaxel using multi-functional polymeric micelles

Natural paclitaxel (Taxol) is an effective anti-cancer drug, although a critical disadvantage is its non-targeting nature. To address this issue, cholesterol-grafted poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-co-undecenoic acid) was synthesized with different starting monomer ratios via a free radical copolymerization route. Folate was subsequently attached to the hydrophilic segment of the polymer in order to target folate receptors-overexpressing cancer cells. The success of synthesis was confirmed with 1H-NMR carried out in CDCl3/D2O. Using a membrane dialysis method, the polymer was then self-assembled into micelles whose hydrophobic cores could be utilized to encapsulate paclitaxel, an extremely hydrophobic compound. The polymer had a low CMC of approximately 20 mg/L in water. Dynamic light scattering further showed that the sizes of blank micelles formed from the polymer were below 180 nm at different pH values tested and approximately 220 nm upon drug incorporation. More importantly, it was demonstrated that the micelles exhibited a useful pH-induced thermo-sensitivity, such that drug was released more rapidly at pH 5.0 (acidic endosomal/lysosomal environment) than at pH 7.4 (normal extracellular pH). In vitro cytotoxicity assays performed against KB cells then provided concluding evidences that the cellular uptake of micelles surface-functionalised with folate was indeed enhanced due to a receptor-assisted endocytosis process. This novel polymeric design thus has the potential to be a useful paclitaxel vehicle for the treatment of folate-receptor positive cancers.