紫杉醇PLA-PEG嵌段共聚物纳米粒腹腔注射的组织分布

分别以嵌段（聚乳酸-聚乙二醇）和非嵌段（聚乳酸）共聚物作为载体材料，采用乳化-液中干燥法制备包载紫杉醇的纳米粒。再以市售注射剂为对照，考察大鼠单剂量腹腔注射7．5mg／kg后，心、肝、脾、肺、肾、髂淋巴结等组织的药物分布情况。以相对摄取率Re、峰浓度比ce和靶向效率Te为指标评价制品的淋巴靶向性。结果表明，两亲性嵌段共聚物纳米粒可明显增强药物淋巴靶向性，并显著减少肝、脾等组织的分布。     

静脉注射用胰岛素三嵌段共聚物纳米粒的制备

目的研究静脉注射用胰岛素三嵌段共聚物纳米粒(Ins-PELGE-NPs)的制备工艺,并考察其影响因素。方法通过复乳/溶剂扩散法制备Ins-PELGE-NPs,并考察其形态、粒径分布、包封率、zeta电位等。结果载药量为4.48%~4.67%的Ins-PELGE-NPs在透射电镜下均呈球形或近球形,分布均匀,平均粒径为140 nm,平均包封率为94%~98%,平均zeta电位为-21.7±4.3 mV。结论所用制备工艺简单、包封率高,可用于系列注射用三嵌段共聚物纳米粒的制备。     

聚乙二醇-聚乳酸-羟基乙酸嵌段共聚物载药纳米粒制备方法的研究进展

目的:为聚乙二醇-聚乳酸-羟基乙酸(PEG-PLGA)嵌段共聚物载药纳米粒制备方法的进一步研究提供参考。方法:以聚乙二醇-聚乳酸-羟基乙酸嵌段共聚物载药纳米粒制备方法PEGPLGAPEG-PLGA等为关键词,组合查询1998年1月-2017年1月在Pub Med、Springer Link、Science Direct、中国知网、万方、维普等数据库中的相关文献,对溶剂挥发法、沉淀法、自乳化溶剂扩散法、盐析法等制备方法进行综述。结果与结论:共检索到相关文献246篇,其中有效文献28篇。虽然载药纳米粒制备方法已经解决了操作、耗能及环境污染上的一些难题,但仍然存在常使用毒性较大含氯有机溶剂和难以工业化大生产等问题。前者可通过寻找毒性较小的有机溶剂(如丙酮、乙酸乙酯)来代替和通过对PLGA结构修饰基团或合成方法的改进使其可溶于毒性较小的有机溶剂加以解决;后者可通过研发新型辅料,或是改进制备工艺(如冻干)来改善纳米粒的稳定性和研发新型生产设备来解决。     

紫杉醇MPEG-PCL纳米粒的制备、表征及其体外释药行为研究

目的 以聚乙二醇单甲醚-聚己内酯(MPEG-PCL)为载体制备紫杉醇MPEG-PCL纳米粒并对其体外释放行为进行考察。方法 采用开环聚合法合成MPEG-PCL共聚物,采用核磁共振波谱仪(¹H-NMR)、傅里叶红外光谱仪(FTIR)对其进行表征;通过共沉淀法制备了紫杉醇MPEG-PCL纳米粒,并测定了粒径分布、Zeta电位、结构特征、包封率以及载药量;同时以磷酸盐缓冲溶液(pH=7.4)为释放介质考察其体外释放行为。结果 成功合成了相对分子质量为4 875的MPEG-PCL共聚物。透射电镜结果显示紫杉醇MPEG-PCL纳米粒具有规则的球形结构,纳米粒的平均粒径为(102.3±3.5)nm,PDI=0.102,药物包封率和载药量分别为(95.6±3.2)%和(8.5±0.4)%。体外释放结果显示紫杉醇可以缓慢的从MPEG-PCL纳米粒中释放出来。结论 MPEG-PCL共聚物是紫杉醇的良好载体,所制备的纳米粒具有包封率和载药量高、药物释放缓慢的特点。     

乳酸-羟基乙酸共聚物纳米粒的制备及其表面修饰

目的:促进生物可降解聚合物乳酸-羟基乙酸共聚物(PLGA)纳米粒作为蛋白、多肽类药物投递载体的应用。方法:综述近几年乳酸-羟基乙酸共聚物纳米粒的制备方法及其参数,并概述其纳米粒的表面修饰手段。结果:乳酸-羟基乙酸共聚物纳米粒的制备方法主要包括乳化-溶剂挥发法、相转变法、乳化-扩散法、沉淀法、盐析法以及高压乳匀法。制备纳米粒的一个关键性参数是表面活性剂/稳定剂。纳米粒表面修饰最常用聚乙二醇。结论:乳酸-羟基乙酸共聚物纳米粒作为一种新型的给药系统富有前景,可广泛应用于亲水性和疏水性药物,尤其是蛋白、疫苗、生物大分子的给药。     

紫杉醇聚丙交酯乙交酯共聚物纳米粒的制备与体外评价

目的采用聚丙交酯乙交酯共聚物（PLGA）载体制备紫杉醇（TAX）纳米粒,并进行体外评价。方法采用改良的溶剂扩散法制备TAX PLGA共聚物纳米粒,考察不同乳化剂类型和各工艺因素对纳米粒粒径的影响,通过动态激光粒度分析仪、透射电子显微镜（TEM）、扫描电子显微镜（SEM）、差示扫描量热法（DSC）及X线粉末衍射（XRD）初步研究其载药性质,并研究纳米粒冻干粉的体外释放特性。结果优选出制备工艺为：双十二烷基二甲基溴化铵（DMAB）作为乳化剂,浓度为1%（W/V）,聚合物浓度为1%（W/V）,水相与有机相的体积比例为20：10,均质机转速为16 000 r•min 1,药物浓度为0.1%（W/V）。所得纳米粒外观圆整,平均粒径为99.0 nm,Zeta电位58.3 mV,包封率为56.77%,载药量率为7.10%。TAX纳米粒具有缓释性,体外释放分为两相。DSC及XRD表明TAX被有效地包裹在纳米粒中。结论PLGA纳米粒可成为TAX的新型载体。     

凝集素修饰乳酸-羟基乙酸共聚物纳米粒的制备及体外黏附性能评价

本文分别以麦胚凝集素、西红柿凝集素和天门冬豌豆凝集素为表面修饰材料，采用碳化二亚胺法制备了不同凝集素修饰的乳酸-羟基乙酸共聚物纳米粒。分别考察了活化剂的用量、活化时间、凝集素的用量、孵化时间对凝集素修饰纳米粒的影响，由此确定最佳制备条件。福林-酚法测定凝集素的修饰率为(18.97±2.9)%～(20.15±2.4)%，纳米粒表面的凝集素浓度为(9.46±1.45)～(10.05±1.19) μg·mg^-1。采用黏蛋白结合法对纳米粒的体外黏附性能进行评价，结果表明纳米粒与黏蛋白溶液在室温下孵化60 min后结合反应达到平衡，此时不同凝集素修饰纳米粒的黏蛋白结合量分别为15.5%，12.1%和11.8%，是普通纳米粒黏蛋白结合量的2.4～3.2倍。经Langmuir方程拟合计算得到各结合速率常数分别为2.373×10^-3，1.536×10^-3和1.714×10^-3 (μg·min/mL)^-1。不同凝集素修饰纳米粒与黏蛋白的结合可被该凝集素的特异性单糖抑制。实验结果表明，与普通纳米粒相比，凝集素修饰纳米粒与黏蛋白的体外黏附能力显著增强，预计其口服后可与胃肠黏膜表面产生黏附作用，从而延长制剂在胃肠道内的滞留时间。     

以叶酸修饰的乳酸-羟基乙酸共聚物为载体的紫杉醇靶向纳米粒的构建与评价

目的 以叶酸修饰的生物可降解材料乳酸-羟基乙酸共聚物(PLGA-PEG-FOL)为载体,构建紫杉醇靶向纳米粒并进行评价。方法 采用乳化-分散法,以溶液稳定性、粒径和包封率为评价指标,通过考察乳化剂的用量、有机相种类、水相与有机相比例、聚合物分子量、药载比、剪切速度等因素对纳米粒制备的影响,确定最优处方和制备工艺,并对纳米粒的形态、粒径、Zeta电位、包封率及载药量进行评价。结果 合成了载体PLGA-PEG-FOL;制备的紫杉醇靶向纳米粒为均匀球形粒子,粒径为(88.2±6.7)nm,Zeta电位为(56.5±4.2)mV,包封率为(92.9±3.2)%,载药量为(4.8±1.3)%。结论 纳米粒制备方法简便易行,重现性好。制备的纳米粒大小均匀,粒度分布较窄,包封率和载药量较高。     

紫杉醇PLGA纳米粒的处方优化与评价

目的 采用生物可降解材料乳酸-羟基乙酸共聚物(PLGA)为载体,比较不同的制备方法和工艺对紫杉醇(PTX)PLGA纳米粒(PTX-PLGA NPs)粒径的影响,筛选出最优制备工艺,并考察所制备纳米粒的体外表征以及对人源胃癌细胞SGC-7901的抗肿瘤效果,为紫杉醇缓释制剂在胃癌中的开发提供一定的实验基础.方法 采用单因...     

冬凌草甲素嵌段共聚物胶束的制备

目的 制备冬凌草甲素单甲醚聚乙二醇-聚乳酸两亲性嵌段共聚物胶束,改善冬凌草甲素的水溶性. 方法以单甲醚聚乙二醇-聚乳酸作为载体,采用丙酮溶剂挥发法和透析法制备不同药物/共聚物投料比的冬凌草甲素嵌段共聚物胶束. 考察胶束相关性质. 以载药量为评价标准,得出最佳投料比. 结果 电镜结果 显示,胶束呈球形或类球形,载药量和包封率受制备方法和投料比的影响. 透析法得到的胶束粒径较小,分散均匀度好,但载药量和包封率偏低. 丙酮溶剂挥发法在药物共聚物的质量比例12.8：25.2时得到的胶束平均粒径为35.675 nm,载药量为22.1%,包封率为65.61%,粒径分布较窄,有利于纳米分散体系的稳定,且对冬凌草甲素有一定的增溶作用. 结论 聚乙二醇-聚乳酸嵌段共聚物胶束能够作为难溶性抗癌药物冬凌草甲素的良好纳米级载体.     

表面修饰紫杉醇纳米粒局部给药抑制血管再狭窄的研究

制备表面修饰紫杉醇纳米粒并观察其抑制兔颈动脉损伤模型新生内膜增生的效果。采用超声乳化-溶剂挥发法制备载紫杉醇纳米粒，用物理吸附法对纳米粒进行表面修饰。对纳米粒进行表征，包封率和体外释放使用高效液相色谱仪进行分析。建立兔颈动脉损伤模型，在血管局部灌注不同浓度的修饰纳米粒。28天后，取出局部给药的颈动脉血管，进行苏木素-伊红(Hematoxylin & Eosin staining，HE)染色和弹力纤维染色。制备的载紫杉醇纳米粒粒径300 nm左右、包封率80%以上且表面带正电荷。体外药物释放呈两相释放。28天后，血管内局部灌注紫杉醇纳米粒悬液可有效抑制血管内皮增生，并呈剂量依赖性。浓度达到30 mg·mL^-1时，可完全抑制血管内膜增生。血管内局部灌注正电荷修饰的紫杉醇纳米粒悬液可有效抑制血管内皮增生，抑制效果随纳米粒悬液浓度的增加而提高。     

Preparation and physicochemical characterization of a novel paclitaxel-loaded amphiphilic aminocalixarene nanoparticle platform for anticancer chemotherapy

Objectives This paper describes the development and optimization of a nanoparticle delivery platform for the anticancer agent, paclitaxel, using a novel amphiphilic carrier, tetrahexyloxy‐tetra‐p‐aminocalix[4]arene (A4C₆). Methods Nanoparticles were successfully prepared at pH 4 by an emulsion evaporation method whereby an organic phase containing paclitaxel : A4C₆ (molar ratio 1 : 10) was dispersed by probe sonication into an aqueous phase containing 0.5% w/v polyvinyl alcohol as stabilizer. Key findings The drug‐loaded nanoparticles had a mean size of 78.7 ± 20.7 nm, surface potential of 38.3 ± 7.67 mV, and paclitaxel loading and encapsulation efficiencies of 69.1 ± 5.3 µg drug/mg carrier and 50.4 ± 3.2%, respectively. Transmission electron micrographs showed discrete particles with no evidence of agglomeration. In‐vitro dissolution into phosphate buffered saline supplemented with 4% bovine serum albumin showed 32.7 ± 3.9%, 82.6 ± 5.3% and 91.0 ± 6.0% of the encapsulated paclitaxel load was released at 5, 72 and 120 h, respectively. Conclusions This is the first report on the use of amino‐substituted amphiphilic calixarenes for the encapsulation of anticancer agents. The nanoparticles produced were significantly smaller than, but had comparable drug loads to the Abraxane nanoparticles, and have the potential to achieve targeted delivery of paclitaxel to tumour tissues.     

阿克他利固体脂质纳米粒的制备及体外释药特性

目的:制备阿克他利固体脂质纳米粒研究外释药模式。方法:单因素考察的基础上,以正交试验设计优化,筛选最佳处方和制备工艺。透射电镜观察固体脂质纳米粒的形态,激光散射测定Zeta电位和粒度分布,超速离心法测定阿克他利固体脂质纳米粒的包封率,研究体外释放速度。结果:所制固体脂质纳米粒外观形态圆整,粒度分布为50~200nm,平均粒径为120nm。Zeta电位为-17.14mV,包封率为51.20%。体外释药特性研究具有良好的缓释特性,在0~12h符合100Q=38.536t1/4-16.859(r=0.999 0),13~648h符合100Q=13.907t1/4 28.32(r=0.999 2)。结论:通过优化处方和制备工艺,采用乳化蒸发-低温固化法制备阿克他利固体脂质纳米粒,其体外释药具有明显的缓释、长效作用。     

紫杉醇两亲嵌段共聚物纳米囊的研究

目的探讨负载紫杉醇的聚乙二醇-b-聚(D,L-乳酸)两亲性嵌段共聚物核-壳型纳米囊(PMT)。方法采用固相分散法制备PMT,动态光散射(DLS)测定PMT的粒径,透射电子显微镜(TEM)和¹HNMR表征PMT的形态,研究共聚物相对分子质量和紫杉醇投药量对PMT的影响,考察PMT对昆明鼠肝癌H22的疗效。结果PMT呈核-壳结构球形,粒径为纳米级,随着PEDLLA中疏水嵌段相对分子质量或载药量的增大而增大,PMT具有与Taxol类似的抑制肿瘤作用。结论本研究为开发紫杉醇新型静脉注射制剂提供了实验依据。     

Tumor necrosis factor alpha blocking peptide loaded PEG-PLGA nanoparticles: preparation and in vitro evaluation

Nanoparticles prepared from polyethyleneglycol-modified poly(d,l-lactide-co-glycolide) (PEG-PLGA-NPs) are being extensively investigated as drug carriers due to their controlled release, biodegradable and biocompatibility. The purpose of this study was to evaluate the in vitro characteristics of PEG-PLGA-NPs loading tumor necrosis factor alpha blocking peptide (TNF-BP). PEG-PLGA copolymer was synthesized by ring-opening polymerization of d,l-lactide, glycolide and methoxypolyethyleneglycol (mPEG) (Mw = 5000). Blank PEG-PLGA-NPs, with particle size within the range of 79.7 to 126.1 nm and zeta potential within the range of -12.91 to -24.55 mV, were prepared by the modified-spontaneous emulsification solvent diffusion (modified-SESD) method. PEG-PLGA-NPs uptake by murine peritoneal macrophages (MPM) was lower than that of PLGA-NPs. TNF-BP was loaded on the blank nanoparticles by electrostatic interactions, and TNF-BP loading capacity of PEG-PLGA-NPs was found to be dependent on the characteristics of blank nanoparticles, peptide concentration and incubation medium. In vitro release experiments showed the peptide release rate affected by the drug loading and ionic strength, and approximately 60.2% of TNF-BP released from nanoparticles still possessed bioactivity. These experimental results indicate that PEG-PLGA-NPs could be used to develop as drug carriers for TNF-BP.     

Effect of preparation conditions on the size and encapsulation properties of mPEG-PLGA nanoparticles simultaneously loaded with vincristine sulfate and curcumin

This study prepared monomethoxy poly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA) nanoparticles simultaneously loaded with vincristine sulfate (Vin) and curcumin (Cur) via O/W emulsion solvent evaporation. Five independent processing parameters were systematically evaluated to enhance the entrapment of dual agents with different properties (i.e. Vin and Cur, which are the hydrophilic and hydrophobic, respectively) into mPEG-PLGA nanoparticles and to control the particle size. The approaches used to investigate the enhancement of drug entrapment efficiencies and control over the particle size included mPEG-PLGA concentration, polyvinyl alcohol (PVA) concentration, initial Vin/Cur content, dichloromethane-to-acetone volume ratio, and aqueous-to-organic phase volume ratio. The nanoparticles produced using the optimum formulation conditions had a particle size of 131.5 nm with a low polydispersity index of 0.047. The entrapment efficiencies were 63.52 ± 2.36% for Vin and 54.60 ± 2.46% for Cur (n = 3). The drug loadings were 1.06 ± 0.04% for Vin and 3.64 ± 0.16% for Cur (n = 3).     

Characterization,in vitro cytotoxicity and cellular accumulation of paclitaxel-loaded lipid nano-emulsions

Lipid nano-emulsions (LNEs) having a mean droplet size of ～50 nm were investigated as drug carriers for paclitaxel (TXL) to achieve its satisfactory loadings and to develop a pharmaceutically acceptable alternative to the current formulation, Taxol®. TXL was incorporated into the LNEs at 2.0 mg/ml without changes in particle size or drug precipitation. In the cytotoxicity study, TXL-loaded LNEs had cytotoxicity to HeLa cells equivalent to that of TXL alone; the 50% growth inhibitory concentrations (IC₅₀) of TXL-loaded LNEs and TXL alone were 1.53 ± 0.23 nM and 1.76 ± 0.08 nM, respectively. However, a cellular accumulation study using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a fluorescent probe showed that the accumulation of DPH-loaded LNEs in HeLa cells was remarkably lower than that of DPH alone. These results indicated that LNEs were a useful vehicle for TXL, even though LNEs themselves could not be efficiently accumulated in HeLa cells.     

瘤内注射用阳离子型紫杉醇乳脂体的制备及体外性质评价

目的:制备适于瘤内给药的阳离子型紫杉醇乳脂体(PTX-CTAB-NES),并对其理化性质及细胞毒性进行评价。方法:采用溶剂蒸发法制备PTX-CTAB-NES,利用中心复合设计优化处方,透射电镜观察形态,纳米粒径仪测定粒径分布,XRD确证PTX在载体中的分散状态,HPLC法测定其包封率、载药量,透析法研究制剂的体外释药行为,并对其细胞毒性进行评价。结果:PTX-CTAB-NES呈类球形,可见明显指纹结构,平均粒径为94.0 nm,Zeta电位为+48.3 mV,包封率、载药量分别为98.0%和3.25%,PTX在载体中以非晶型状态存在。与Taxol注射液相比,阳离子型紫杉醇乳脂体具有明显的缓释作用,对MCF-7人乳腺癌细胞的IC50降低。结论:PTX-CTAB-NES正电性强,包封率高,缓慢释放药物,细胞毒性大,是瘤内原位给药的理想载体。     

紫杉醇固体脂质纳米粒大鼠体内药动学

目的研究紫杉醇固体脂质纳米粒在大鼠体内的药动学。方法10只健康大鼠,雌雄各半,分为2组,分别口服给药紫杉醇固体脂质纳米粒和紫杉醇乳剂30 mg.kg-1,在设计的时间点从颈静脉取血,采用RP-HPLC测定紫杉醇在全血中的药物浓度,药动学参数用3P97软件进行处理。结果大鼠口服给药后,紫杉醇固体脂质纳米粒和乳剂的tm ax分别为3.133 h和1.627 h,MRT分别为10.362 h和3.297 h,mρax分别为1.512 2 mg.L-1和0.718 9 mg.L-1。结论固体脂质纳米粒能够显著改善大鼠体内紫杉醇的药动学行为,有利于其更好地发挥抗肿瘤作用。     

Principal component and causal analysis of structural and acute in vitro toxicity data for nanoparticles

Structure toxicity relationship analysis was conducted using principal component analysis (PCA) for a panel of nanoparticles that included dry powders of oxides of titanium, zinc, cerium and silicon, dry powders of silvers, suspensions of polystyrene latex beads and dry particles of carbon black, nanotubes and fullerene, as well as diesel exhaust particles. Acute in vitro toxicity was assessed by different measures of cell viability, apoptosis and necrosis, haemolytic effects and the impact on cell morphology, while structural properties were characterised by particle size and size distribution, surface area, morphology, metal content, reactivity, free radical generation and zeta potential. Different acute toxicity measures were processed using PCA that classified the particles and identified four materials with an acute toxicity profile: zinc oxide, polystyrene latex amine, nanotubes and nickel oxide. PCA and contribution plot analysis then focused on identifying the structural properties that could determine the acute cytotoxicity of these four materials. It was found that metal content was an explanatory variable for acute toxicity associated with zinc oxide and nickel oxide, while high aspect ratio appeared the most important feature in nanotubes. Particle charge was considered as a determinant for high toxicity of polystyrene latex amine.