共查询到19条相似文献,搜索用时 316 毫秒
1.
背景:紫杉醇临床用剂型紫素易引起过敏反应,因此研制新的紫杉醇新剂型就显得十分有意义。
目的:研制紫杉醇新剂型,观察其在动物模型上治疗肿瘤的效果。
方法:合成具有自主知识产权的生物可降解材料医用聚己内酯。采用溶剂替代法制备载紫杉醇纳米粒子,对其粒径、形态、紫杉醇含量、体外释放等进行测定。选用TA2系实验小鼠,建立乳腺癌动物模型,随机分为5组,分别局部注射生理盐水、紫素、低剂量、中剂量及高剂量紫杉醇纳米粒子进行治疗。
结果与结论:实验制备的紫杉醇纳米粒子平均粒径约为153.54 nm,包埋率为87.25%,紫杉醇含量19.06%。体外可恒定释放30 d以上。2周药物治疗显示,各治疗组均不同程度上抑制了肿瘤的生长,其中紫杉醇纳米粒子中、高剂量组的抑瘤率明显高于紫素治疗组(P < 0.01)。提示紫杉醇纳米粒子可缓释药物,中剂量组和高剂量组对小鼠乳腺癌的抑瘤率高于紫素组。关键词:紫杉醇;医用聚己内酯;纳米粒子;乳腺癌;缓释药物
缩略语注释:HPLC:high performance liquid chromatography,高效液相色谱
doi:10.3969/j.issn.1673-8225.2012.16.005 相似文献
2.
《中国组织工程研究》2010,(8)
背景:目前研究使用的聚氰基丙烯酸烷基酯,在降解过程中生成了醛类化合物,易导致一定程度的毒性与刺激作用。课题组在氰基丙烯酸酯单体中引入乙二醇取代基,合成一种新的与人体细胞结构更相容的纳米胶束载体材料—聚氰基丙烯酸乙二酯聚合物,作为脂溶性药物载体具有光明的应用前景。目的:以聚氰基丙烯酸乙二酯聚合物为载体,制备紫杉醇-聚氰基丙烯酸二乙酯纳米胶束,验证其用于小鼠乳腺癌治疗的可接受性。方法:超声乳化法制备不同粒径紫杉醇-聚氰基丙烯酸二乙酯纳米胶束并进行表征;建立BablC小鼠乳腺癌动物模型,分为生理盐水组和空白纳米胶束组,紫素阳性对照组,高、中、低3个紫杉醇-聚氰基丙烯酸纳米胶束剂量治疗组。对瘤体进行局部注射给药,检测紫杉醇-聚氰基丙烯酸二乙酯纳米胶束对肿瘤的抑制效果。结果与结论:紫杉醇-聚氰基丙烯酸二乙酯纳米胶束平均粒径70nm,药物含量为19.89%,药物体外释放能够持续达到2周以上时间。动物实验表明,在相当紫杉醇总量为30,60,90mg/kg的3种剂量下,紫杉醇-聚氰基丙烯酸二乙酯纳米胶束给药组与生理盐水组相比具有明显的抑瘤效果(P0.001),抑瘤率分别为68.49%,77.03%和81.87%。提示紫杉醇-聚氰基丙烯酸二乙酯纳米胶束作为小鼠乳腺癌治疗的缓释制剂治疗效果显著,具有良好的可接受性。 相似文献
3.
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. 相似文献
4.
《中国组织工程研究》2010,(8)
背景:原发性肝癌的手术切除率较低,肝癌的局部治疗成为重要手段。经皮微波消融治疗能达到原位灭活的目的,但不能彻底杀灭瘤细胞。缓释剂型化疗药物可形成局部较高药物浓度及发挥较持久作用,目前已多被应用于原发性肝癌的治疗。目的:观察负载表柔比星的壳聚糖微球联合微波消融局部治疗荷肝癌小鼠皮下移植瘤的效果。方法:采用W/O型乳化-固化法制备表柔比星-壳聚糖微球,扫描电镜观察壳聚糖微球的表面形态,粒径大小。紫外分光光度计分析载药微球的包封率、载药量及药物累积释放率。将24只H22皮下肝癌荷瘤小鼠分成4组,各组皮下肝癌肿瘤分给予以下治疗:单纯微波治疗;微波治疗后第2天给予瘤内注射生理盐水;微波治疗后给予瘤内注射表柔比星;微波治疗后联合瘤内注射载药微球,监测荷瘤小鼠肿瘤体积变化并计算抑瘤率。结果与结论:壳聚糖微球平均粒径约为105μm,粒径大小较一致,包封率约为80%,载药率约为11%,2周的累积缓释率为84%。微波联合瘤内注射生理盐水、表柔比星、载药微球的抑瘤率分别为8%,20%,47%。表明壳聚糖微球是一种有效的表柔比星局部缓释剂型,联合微波消融治疗有较强的抑瘤作用。 相似文献
5.
目的利用聚己内酯(PCL)生物可降解高分子材料与普朗尼克F68(Pluronic F68,F68)共混物作为载体材料与抗癌药物紫杉醇(paclitaxel,PTX)组成微球控释系统,并对其在小鼠体内的抗肿瘤活性进行研究。方法采用乳化-溶剂挥发法制备紫杉醇微球,研究PCL/F68载药微球及PCL载药微球的体外释放并用扫描电子显微镜比较微球表面形态,考察PCL/F68载药微球对小鼠肝癌H22实体瘤和腹水瘤的抗肿瘤活性并与紫杉醇注射液进行比较。结果紫杉醇的包封率约为90%。扫描电镜结果显示微球球形圆整,PCL微球表面光滑,而PCL/F68微球表面粗糙,呈现多孔状(Fig 1)。体外释放实验表明紫杉醇微球有明显的缓释性能。 相似文献
6.
目的载紫杉醇聚乳酸聚羟基乙酸共聚物(PLGA)/F68纳米粒逆转耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞多药耐药的可行性研究。方法使用超声乳化溶剂挥发法分别制备载紫杉醇PLGA和载紫杉醇PLGA/F68纳米粒(10%),并对载紫杉醇纳米粒进行表征。载紫杉醇纳米粒的体外释放研究使用高效液相色谱进行分析。最后研究载紫杉醇纳米粒在耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞的细胞摄取和细胞毒性(PLGA/F68组、PLGA组和泰素组)。结果纳米粒呈球形,表面粗糙多孔,平均粒径250 nm左右,粒径分布比较窄,体外药物释放呈双相释放模型。载紫杉醇PLGA/F68纳米粒能够被耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞摄取。载紫杉醇PLGA/F68纳米粒比载紫杉醇PLGA纳米粒(P〈0.05)和泰素(TaxolR)(P〈0.05)有更高的细胞毒性。结论载紫杉醇PLGA/F68纳米粒能够逆转耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞的多药耐药,药用辅料Pluronic F68在乳腺癌治疗中具有潜在的应用前景。 相似文献
7.
目的制备表皮生长因子(EGF)微球并对其生物学活性进行评价。方法利用改进的复乳法.以聚乳酸,羟基乙酸共聚物(PLGA)作为载体,制备EGF微球。检测EGF微球形貌表征、微球粒径分布、载药率、包封率和释药行为。用噻唑蓝(MTr)法测定增殖度,研究不同浓度EGF微球对细胞增殖能力的影响,研究相同浓度不同剂型EGF对细胞增殖的影响.研究微球载体的安全性。结果EGF微球粒径约为200nm,粒径分布比较均一,微球之间无粘连,分散性好。载药率为0.02%.包封率为85%。释药符合释放动力学模型,释放长达24h。不同浓度EGF微球均促进细胞增殖。其中10μg/L为最适质量浓度(与对照组EE,P〈0.01)。质量浓度10μg/L时,EGF微球组与EGF原液组相比差异有统计学意义(P〈0.01)。不同质量浓度空微球对细胞没有毒性,不影响细胞增殖(组间没有差异,P〉0.05)。结论成功制备EGF微球。细胞实验证明EGF微球制备过程中EGF保持原有活性。与EGF原液比较.EGF微球促进细胞增殖能力更强,微球载体对细胞没有毒性作用。 相似文献
8.
目的 研究氟维司群的用药剂量对雌激素受体阳性乳腺癌晚期患者疗效的影响。方法 选取2018年3月~2019年3月本院收治并诊断为雌激素受体阳性乳腺癌晚期患者60例,随机分为高剂量组(n=25)和低剂量组(n=35)。高剂量组给予500 mg氟维司群治疗,低剂量组给予250 mg氟维司群治疗。比较两组临床治疗效果,不良反应及无进展生存时间(PFS)。结果 高剂量组的ORR与CBR均高于低剂量组[12.00% vs 11.43%,52.00% vs 45.72%],但差异无统计学意义(P>0.05)。高剂量组的PFS为5.5个月,低剂量组的PFS为4.9个月,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论 高剂量(500 mg)氟维司群对处于晚期的雌激素受体阳性乳腺癌患者的生存有一定的改善作用,未增加不良反应的发生。 相似文献
9.
柠檬黄对雄性小鼠生殖细胞的影响 总被引:1,自引:0,他引:1
探讨柠檬黄对雄性小鼠生殖细胞的影响。选择成年雄性小鼠分别给予柠檬黄0.25 g/kg(低剂量组)、0.5 g/kg(中剂量组)和1 g/kg(高剂量组),连续灌胃染毒5 d,通过小鼠精子畸形率、精细胞微核率以及睾丸形态变化等方面来评价柠檬黄对生殖细胞的影响。与对照组相比,高剂量组的柠檬黄能引起小鼠精子的畸形率和精细胞微核率升高(P〈0.05),而中、低剂量组没有明显的变化(P〉0.05)。睾丸组织切片显示,低、中剂量组与对照组相比没有明显改变,高剂量组小鼠睾丸生精小管管腔内可见精子数量减少,生精上皮细胞层次减少,部分细胞有浓缩、溶解等坏死样变。高浓度的柠檬黄能使雄性小鼠精子畸形率增加,并造成雄性小鼠精细胞微核率上升,有一定的致突变性。 相似文献
10.
目的:通过本实验研究探讨孕妇禁忌中药商陆(Phytolacca acinosa)对小鼠骨髓嗜多染红细胞微核频率的影响。方法:先用体重18-22g的雌性昆明小鼠,随机分为10组,即阴性(灌胃生理盐水)、阳性(腹腔注射环磷酰胺)对照组、各实验组用生药商陆及醋制商陆煎液分别以四个剂量组(I、Ⅱ、Ⅲ、Ⅳ)每天灌胃1次,5天后取骨髓观察嗜多染红细胞的微核率。结果:两种商陆水煎剂的I、Ⅱ剂量组诱发小鼠微核率虽有数目变化,但无统计学意义,且与阴性对照组相比;P>0.05,与阳性对照组相比均有显著差异,P<0.01。而Ⅲ、Ⅳ剂量组诱发微核率与阴性对照组相比:P<0.01,与阳性对照组相比无显著差异。讨论:本实验结果提示孕妇禁忌中药商陆诱发小鼠微核率具有明显的剂量效应关系。因此,在临床应用药时,特别是育龄妇女更应慎重。 相似文献
11.
Radiosensitization of paclitaxel, etanidazole and paclitaxel+etanidazole nanoparticles on hypoxic human tumor cells in vitro 总被引:2,自引:0,他引:2
Paclitaxel and etanidazole are hypoxic radiosensitizers that exhibit cytotoxic action at different mechanisms. The poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel, etanidazole and paclitaxel+etanidazole were prepared by o/w and w/o/w emulsification-solvent evaporation method. The morphology of the nanoparticles was investigated by scanning electron microscope (SEM). The drug encapsulation efficiency (EE) and release profile in vitro were measured by high-performance liquid chromatography (HPLC). The cellular uptake of nanoparticles for the human breast carcinoma cells (MCF-7) and the human carcinoma cervicis cells (HeLa) was evaluated by transmission electronic microscopy and fluorescence microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical shape with size between 80 and 150 nm. The EE was higher for paclitaxel and lower for etanidazole. The drug release was controlled over time. The cellular uptake of nanoparticles was observed. Co-culture of the two tumor cell lines with drug-loaded nanoparticles demonstrated that released drug effectively sensitized hypoxic tumor cells to radiation. The radiosensitization of paclitaxel+etanidazole nanoparticles was more significant than that of single drug-loaded nanoparticles. 相似文献
12.
目的 制备紫杉醇纳米粒子,并考察其在实验兔体内经DispatchTM球囊灌注后组织分布情况.方法 以生物可降解材料聚乳酸聚乙醇酸共聚物(PLGA)为原料,采用超声乳化-溶剂挥发法制备载紫杉醇纳米粒子.对纳米粒子的粒径、形态、药物含量和体内外释放进行测定.通过新西兰兔腹主动脉局部给药模型考察紫杉醇纳米粒子球囊灌注后组织分布情况.结果 制备的紫杉醇纳米粒子的平均粒径约为246 nm,包封率为93.25%,紫杉醇含量19.06%.体外可维持恒定释放30d以上.新西兰兔体内经腹主动脉实现DispatchTM球囊灌注,观察药物可在靶部位体内贮留长达21d.结论 紫杉醇PLGA纳米粒子作为一种局部药物传递系统,经球囊灌注在动物模型体内提高局部药物浓度,延长药物作用时间,可实现缓释靶向治疗. 相似文献
13.
pH-Sensitive poly(N,N-dimethylaminoethyl methacrylate (DMAEMA)/2-hydroxyethyl methacrylate (HEMA)) nanoparticles were prepared for the triggered release of paclitaxel within a tumor microenvironment. Tumors exhibit a lower extracellular pH than normal tissues. We show that paclitaxel release from DMAEMA/HEMA particles can be actively triggered by small, physiological changes in pH (within 0.2-0.6 pH units). Monodispersed nanoparticles were synthesized by forming an O/W emulsion followed by photopolymerization. Particles were characterized by transmission electron microscopy, dynamic light scattering, electrophoresis, and cytotoxicity. High release rates and swelling ratios are achieved at low pH, low crosslinking density, and high content of DMAEMA. Paclitaxel release is limited to 9% of the payload at pH 7.4 after a 2-h incubation at 37 degrees C. After adjusting to pH 6.8, 25% of the payload is released within 2h. Cell viability studies indicate that pH-sensitive DMAEMA/HEMA nanoparticles are not cytotoxic and may be used as an efficient, feedback-regulated drug delivery carrier. 相似文献
14.
紫杉醇聚己内酯/泊洛沙姆188载药纳米粒及其抗肿瘤活性 总被引:1,自引:0,他引:1
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, 相似文献
15.
Paclitaxel is one of the best anticancer drugs, which has excellent therapeutic effects against a wide spectrum of cancers. The formulation of paclitaxel used in its currently clinical administration includes Cremophor EL, which has been found to cause serious side effects. Nanoparticle formulation of paclitaxel may provide an ideal solution for this problem and achieve a sustained chemotherapy. A novel copolymer, poly(lactide)-vitamin E TPGS (PLA-TPGS), was synthesized from lactide and d-alpha-tocopheryl polyethylene glycol 1000 succinate by bulk polymerization for nanoparticle formulation of anticancer drugs. 1H NMR, FTIR and GPC were used to detect molecular structure of the copolymer. Paclitaxel-loaded PLA-TPGS nanoparticles were fabricated by a modified solvent extraction/evaporation technique with or without emulsifier involved, which were characterized by laser light scattering for size and size distribution; field emission scanning electron microscopy for surface morphology; zeta potential for surface charge; X-ray photoelectron spectroscopy for surface chemistry. The drug encapsulation efficiency and the in vitro drug release kinetics were measured by high-performance liquid chromatography. Formulation optimization was pursued. The particles were found of around 300 nm in size and narrow size distribution. Of all, 89% drug encapsulation efficiency has been achieved for nanoparticles of 5% drug loading. The drug release from PLA-TPGS nanoparticles was found to be biphasic with an initial burst of 17% in the first day, followed by a sustained pattern with 51% release after 31 days. 相似文献
16.
Paclitaxel-loaded poly(gamma-glutamic acid)-poly(lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer 总被引:6,自引:0,他引:6
The study was to develop paclitaxel-loaded formulations using a novel type of self-assembled nanoparticles (P/NPs) composed of block copolymers synthesized by poly(gamma-glutamic acid) and poly(lactide). For the potential of targeting liver cancer cells, galactosamine was conjugated on the prepared nanoparticles (Gal-P/NPs). In the in vitro studies, it was found that both the P/NPs and the Gal-P/NPs had a similar release profile of paclitaxel. The activity in inhibiting the growth of HepG2 cells by the Gal-P/NPs was comparable to that of a clinically available paclitaxel formulation (Phyxol), while the P/NPs displayed a significantly less activity (p<0.05). The biodistribution and anti-tumor efficacy of the prepared nanoparticles were studied in hepatoma-tumor-bearing nude mice. It was found that the groups injected with Phyxol, the P/NPs or the Gal-P/NPs significantly delayed the tumor growth as compared to the control group injected with PBS (p<0.05). Among all studied groups, the group injected with the Gal-P/NPs appeared to have the most significant efficacy in the reduction of the size of the tumor. This is because a large number of the Gal-P/NPs were observed at the tumor site, and subsequently released their encapsulated paclitaxel to inhibit the growth of the tumor. The aforementioned results indicated that the Gal-P/NPs prepared in the study had a specific interaction with the hepatoma tumor induced in nude mice via ligand-receptor recognition. Therefore, the prepared Gal-P/NPs may be used as a potential drug delivery system for the targeted delivery to liver cancers. 相似文献
17.
Farnaz Dabbagh Moghaddam Somayeh Hamedi Mehrouz Dezfulian 《Comparative clinical pathology》2016,25(5):947-952
This study investigated anti-tumor effect of C-phycocyanin from Anabaena sp.ISC55 on breast cancer in inbred BALB/c mice; 50 adult BALB/c inbred mice with injection of 4T1 breast cancer cell line were examined. Animals were classified into six groups of treatment and control. Two doses of phycocyanin were considered in the treatment groups; the main dose was 10-mg/kg body weight, and the second dose was 150-mg/kg body weight. Paclitaxel was used at a dose of 100.0-mg/kg body weight as comparative control drug. Microscopic examination on mammary tissue after 14 days in the treatment group with high dose of Anabaena phycocyanin (concentration of 150 μL) revealed histopathological regression of tumor (p < 0.05), with plenty of apoptotic cells in epithelium of the mammary ducts. In contrast, mice in group with low dose of Anabaena phycocyanin showed mild mononuclear cell infiltration in to the mammary tissue. There were few nests of epithelial cells with moderate mitotic activity and pleomorphism. In the paclitaxel group, mild inflammation in connective tissue with rare apoptotic cells, low mitotic activity, and moderate pleomorphism of tumor cells were seen. The present study suggested that high dose of phycocyanin as an effective anti-tumor product can potentially reduce proliferation and enhanced apoptosis in tumor cells. So it is useful to develop a new way for the treatment of cancer. 相似文献
18.
Poly(d,l-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs 总被引:4,自引:0,他引:4
This research developed a novel bioadhesive drug delivery system, poly(d,l-lactide-co-glycolide)/montmorillonite (PLGA/MMT) nanoparticles, for oral delivery of paclitaxel. Paclitaxel-loaded PLGA/MMT nanoparticles were prepared by the emulsion/solvent evaporation method. MMT was incorporated in the formulation as a matrix material component, which also plays the role of a co-emulsifier in the nanoparticle preparation process. Paclitaxel-loaded PLGA/MMT nanoparticles were found to be of spherical shape with a mean size of around 310 nm and polydispersity of less than 0.150. Adding MMT component to the matrix material appears to have little influence on the particles size and the drug encapsulation efficiency. The drug release pattern was found biphasic with an initial burst followed by a slow, sustained release, which was not remarkably affected by the MMT component. Cellular uptake of the fluorescent coumarin 6-loaded PLGA/MMT nanoparticles showed that MMT enhanced the cellular uptake efficiency of the pure PLGA nanoparticles by 57-177% for Caco-2 cells and 11-55% for HT-29 cells, which was dependent on the amount of MMT and the particle concentration in incubation. Such a novel formulation is expected to possess extended residence time in the gastrointestinal (GI) tract, which promotes oral delivery of paclitaxel. 相似文献
19.
Seong Deok Kong Marta Sartor Che-Ming Jack Hu Weizhou Zhang Liangfang Zhang Sungho Jin 《Acta biomaterialia》2013,9(3):5447-5452
Stimuli-responsive nanoparticles (SRNPs) offer the potential of enhancing the therapeutic efficacy and minimizing the side-effects of chemotherapeutics by controllably releasing the encapsulated drug at the target site. Currently controlled drug release through external activation remains a major challenge during the delivery of therapeutic agents. Here we report a lipid–polymer hybrid nanoparticle system containing magnetic beads for stimuli-responsive drug release using a remote radio frequency (RF) magnetic field. These hybrid nanoparticles show long-term stability in terms of particle size and polydispersity index in phosphate-buffered saline (PBS). Controllable loading of camptothecin (CPT) and Fe3O4 in the hybrid nanoparticles was demonstrated. RF-controlled drug release from these nanoparticles was observed. In addition, cellular uptake of the SRNPs into MT2 mouse breast cancer cells was examined. Using CPT as a model anticancer drug the nanoparticles showed a significant reduction in MT2 mouse breast cancer cell growth in vitro in the presence of a remote RF field. The ease of preparation, stability, and controllable drug release are the strengths of the platform and provide the opportunity to improve cancer chemotherapy. 相似文献