普鲁兰多糖的硬脂酸修饰及其作为纳米药物载体的研究

利用1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)和4-二甲氨基吡啶(DMAP)催化硬脂酸(SA)与具有良好生物相容性的普鲁兰多糖(Pullulan)反应, 将硬脂酸接枝在普鲁兰分子链的羟基上, 得到取代度不同的疏水改性两亲性普鲁兰多糖衍生物PUSA1, PUSA2 及PUSA3, 其临界胶束浓度分别为50, 32, 18 μg/mL; 透射电镜(TEM)图像显示透析法制备的PUSA 自组装颗粒为球形. 以阿霉素为模型药物制备了PUSA 载药纳米粒, 考察了载药纳米粒的载药量、包封率和体外药物释放. 结果表明PUSA3 的包封率高达84%, 载药量达7.79%. 药物可在37 ℃, pH＝7.4 的PBS 溶液中持续释放90 h 以上. 细胞毒性实验(MTT)结果显示当PUSA 的浓度高达1000 μg/mL 时48 h 后细胞存活率依然在90%左右. 流式细胞及荧光分析表明载药纳米粒的细胞摄取率远远高于游离药物. 说明PUSA 是一种新型的有潜在应用价值的药物载体材料.     

肝靶向海藻酸钠载药纳米粒的细胞毒性研究

本研究将具有肝靶向性分子甘草次酸（GA）偶联在具有生物相容性和生物可降解性的天然高分子海藻酸钠（ALG）上,合成了甘草次酸改性的海藻酸钠（GA—ALG）;对广谱抗癌药物阿霉素（DOX）进行包封,制备了肝靶向载药纳米粒,并考察了GA—ALG载药纳米粒的体外释药性能和对肝癌细胞的抑制作用．利用核磁、红外和元素分析技术对GA—ALG结构和GA取代度进行了表征;对GA—ALG载药纳米粒的形貌、粒径、表面Zeta电位等进行了测定,结果显示纳米粒具有较规则球形结构,其水合粒径为（214±11）nm．GA—ALG载药纳米粒在模拟生理条件下（pH7．4）可持续释药长达20天;MTT结果显示GA-ALG载药纳米粒对7703肝癌细胞的具有明显的杀伤作用．     

阿霉素-姜黄素纳米递药系统制备及体外缓释研究

基于点击反应,高效合成具有pH响应性和高载药率的己烷-1,6-二丙炔酸二酯共交联阿霉素、姜黄素主链型纳米递药系统,并采用紫外光谱、红外光谱、粒度仪、Zata电位、透射电镜进行结构及形貌表征,并考察其在不同pH条件的缓释行为,监测纳米粒降解后的形态学变化。结果表明：所制材料为双药共载均匀球形纳米粒,粒径100～200 nm。通过pH响应化学键实现对药物“智能”化控制释放。纳米粒所载阿霉素的包封率49.7%,载药率59.4%;姜黄素的包封率41.1%,载药率35.7%。缓释曲线显示：随环境pH降低,药物释放率增大,粒径分布变宽,电镜观察形貌从均匀球形变成“树枝状”;而在正常生理条件下药物基本不释放。实验表明该纳米递药系统具有良好的肿瘤微环境pH响应及缓控释性能。     

可生物降解固体脂质纳米粒的制备、表征及药物的体外释放

以可生物降解材料硬脂酸为载体, 以葛根总黄酮为模型药物, 采用乳化蒸发-低温固化法制备固体脂质纳米粒. 采用透射电镜研究载药纳米粒形态, 激光粒度分析仪测定其粒径, X射线衍射仪进行物相鉴别, 并对纳米粒的包封率及体外释药特性等进行了研究. 分析结果表明, 所制备硬脂酸固态脂质纳米粒为类球实体, 粒径分布比较均匀, 平均粒径为(263.82±3.6) nm, 包封率为(67.53±0.12)%. X射线衍射分析证明药物以分子或细小粒子分散于脂质骨架中. 体外释药研究结果表明, 纳米粒体外释药先快后慢, 12 h累积释药50%, 包封于降解材料骨架内的药物通过骨架溶蚀缓慢释放. 药物的体外释放符合Higuchi方程.     

细胞内氧化还原响应型肝靶向嵌段聚合物的合成及纳米自组装性能

通过两步可逆加成-断裂链转移自由基聚合(RAFT)和缩醛脱保护反应合成了一种亲水段含半乳糖侧基和疏水段含吡啶环二硫键侧基的两亲性嵌段聚合物PMAIg GP-b-PPDSMA(PMg PP),用核磁共振氢谱(~1H NMR)和凝胶渗透色谱(GPC)分析验证了目标产物的化学结构.利用纳米沉淀技术和巯基氧化自交联反应制备内核二硫键交联的PMg PP纳米粒(PMg PP-CC NPs).动态光散射(DLS)和透射电子显微镜(TEM)测定结果表明,PMg PP-CC NPs粒径较小(30 nm),且粒径分布较窄.在谷胱甘肽(GSH)还原环境下,PMg PPCC NPs粒径不断增大,发生了解组装.以阿霉素(DOX)为模型药物制备了PMg PP-CC/DOX NPs,载药量可达12.5%,对应包封率为83.3%,其粒径与空白PMg PP-CC NPs粒径大小相近,且粒径分布均匀.体外药物释放实验表明,PMg PP-CC/DOX NPs在体液条件下46 h释放了4.47%的DOX,而在10 mmol/L GSH条件下累积释放量达到了50.6%.细胞胞吞实验进一步验证了PMg PP-CC/DOX NPs可高效入胞并在细胞内快速释放DOX.体外细胞毒性(MTT)实验表明,PMg PP-CC/DOX NPs对肝癌Hep G-2细胞表现出良好的增殖抑制活性.因此,多功能PMg PP-CC NPs在实现肝靶向纳米精准给药上呈现出良好的应用前景.     

靶向纳米钻石-甲氨蝶呤药物体系制备及与MCF-7细胞作用

以羧基化纳米钻石(ND-COOH)为基体, 通过共价键合方法将聚乙二醇二胺(H₂N-PEG-NH₂)、 叶酸(FA)和缩水甘油(GLY)偶联于ND-COOH表面, 赋予纳米钻石载体较好的水溶分散性和靶向性, 借助氢键和范德华力等作用力负载甲氨蝶呤(MTX), 得到靶向纳米钻石-聚乙二醇二胺-叶酸/缩水甘油/甲氨蝶呤(ND-PEG-FA/GLY/MTX NPF/G/M)纳米药物体系. 采用透射电子显微镜、 X射线能量色散谱、 粒径及电位测试证实已制备NPF/G/M. 体外释药发现NPF/G/M在肿瘤环境(pH=5.5)中的药物释放量为正常生理环境(pH=7.4)中的3倍, 表明其具有良好的药物输送特性. 此外, 利用流式细胞术和MTT毒性测试探究了MCF-7细胞摄取NPF/G/M的机制及动力学特性和细胞毒性, 结果表明NPF/G/M以依赖能量、 温度、 网格蛋白、 小窝蛋白和叶酸受体介导的机制进入细胞, 从而将药物缓慢释放于细胞内, 进而诱导细胞凋亡. 研究结果表明, NPF/G/M可作为一种良好的药物输送体系, 为其应用于乳腺癌的临床治疗提供理论参考.     

叶酸修饰星型端氨基PEG-PLGA纳米胶束的制备及肿瘤细胞靶向作用

合成了星型多臂端氨基聚乙二醇(PEG)/聚乳酸-羟基乙酸(PLGA)两亲性嵌段共聚物(4s-PLGA-PEG-NH₂), 并通过核磁共振和凝胶渗滤色谱法对其结构进行表征; 采用溶剂挥发法制备阿霉素载药纳米胶束, 利用EDC缩合法与叶酸偶联, 得到叶酸修饰的星型端氨基PEG-PLGA纳米胶束; 采用动态光散射、 紫外光谱及透射电镜等手段对纳米胶束进行了表征; 对载药纳米胶束在HeLa细胞中的摄取及细胞毒性进行了初步评价. 结果表明, 经叶酸修饰的星型多臂端氨基PEG-PLGA载药纳米胶束可有效提高HeLa细胞的摄取率以及对HeLa细胞的杀伤率, 表明其可作为一类新型的靶向抗肿瘤药物递送载体.     

基于碳点多功能纳米载药体系的制备及pH响应释药性能研究

采用一步微波法成功制备了表面带氨基的荧光纳米碳点CDots, 并通过酰胺化反应将靶向基团叶酸接枝到碳点表面, 成功获得中间产物CDots-FA. 在此基础上, 通过已合成四臂端酰肼基化合物2与抗肿瘤药物阿霉素(DOX)连接, 实现在碳点表面的阿霉素药物分子的化学键合, 最终获得多功能纳米载药体系DOX-CDots-FA. 利用原子力显微镜(AFM)、高分辨透射电镜(HR-TEM)和荧光光谱仪对荧光纳米碳点CDots的性能进行表征, 并通过核磁共振、紫外-可见吸收光谱对DOX-CDots-FA结构、接枝率进行了表征. 同时对纳米载药体系DOX-CDots-FA体外药物释放行为、细胞毒性及细胞摄取成像进行了系统的研究. 结果表明, DOX-CDots-FA具有良好的pH响应性. 叶酸靶向基团能加速DOX-CDots-FA被HeLa (FR+)细胞摄取, 并表现出更强的细胞毒性. 同时细胞摄入成像实验表明, 在叶酸靶向作用下, DOX-CDots-FA通过内吞作用进入HeLa细胞, 随后阿霉素被释放出来并进入细胞核区域, 抑制细胞的生长, 从而实现靶向治疗, 降低毒副作用.     

NaYF_4:Yb/Er-碳纳米管功能纳米材料的制备、表征及其在肿瘤细胞的靶向检测和治疗中的应用

将叶酸分子(FA)和2,3-二巯基丁二酸(DMSA)修饰的稀土上转换发光纳米粒子NaYF4:Yb/Er通过酰胺键偶联在多壁碳纳米管(MWCNT)的表面,得到NaYF4:Yb/Er-MWCNT-FA功能化复合纳米材料,并通过透射电子显微镜(TEM)、X射线衍射(XRD)、紫外-可见吸收光谱(UV-vis)、荧光光谱(PL)和共聚焦激光扫描显微镜等手段表征了其形貌、结构、发光性能和靶向成像性能.共聚焦激光扫描显微镜结果表明,相对于正常的HLF细胞,所制备的复合材料能够靶向检测叶酸受体高表达的宫颈癌Hela细胞.此外,将阿霉素进一步通过ππ堆垛吸附在此复合材料后,该载药体系具有明显的抗肿瘤活性,能够实现对肿瘤细胞的一步检测和治疗.     

pH敏感型mPEG-Hz-PLA聚合物纳米载药胶束的制备

以合成的含有腙键的聚乙二醇大分子(mPEG-Hz-OH)为引发剂,以丙交酯为单体引发开环聚合反应,并通过调整投料比,制备出3种不同分子量的含腙键的生物可降解嵌段聚合物(mPEG-Hz-PLA).将腙键引入到聚合物的骨架中,以此构建聚合物胶束并作为pH敏感型纳米药物载体.制备的pH敏感型胶束的CMC值等于或低于5.46×10-4 mg/m L,DLS和TEM显示粒径均小于100 nm,且粒径分布均匀.非pH敏感型胶束在不同pH下的粒径变化不明显,而pH敏感型胶束在酸性环境下(pH=4.0和pH=5.0)胶束粒径出现了明显变化.以阿霉素为模型药物制备了pH敏感型载药胶束,其粒径比空白胶束大(100~200 nm),且粒径分布均匀.药物释放实验表明pH敏感型载药胶束随着释放介质pH降低累积释药量增高.MTT实验表明空白胶束对HeLa细胞和RAW264.7细胞几乎没有抑制作用,而载阿霉素的胶束对2种细胞的抑制作用都随着剂量的增大和时间的延长而增强.     

Studies on the mechanical and friction properties of polyamide 6-Cu/Si nanocomposites

Polyamide 6 nanocomposites reinforced with Cu/Si nanoparticles (PA6-Cu/Si) were prepared by the in-situ ring-opening polymerization of ?-caprolactam. The in-situ polymerization was critical for preventing the aggregation of Cu/Si nanoparticles. The Cu/Si nanoparticles in the nanocomposite retained their nano characteristics and were not oxidized by the amino groups in PA6. The structure of the as-fabricated PA6-Cu/Si nanocomposite was evaluated by transmission electron microscopy (TEM), X-ray diffraction (XRD), and ultraviolet-visible absorption spectroscopy (UV-vis). The friction and wear resistance, mechanical strength, and antistatic performance of PA6-Cu/Si were also evaluated. The PA6 polymer chains prevent the Cu/Si nanoparticles from aggregation by coating the surface of the Cu/Si nanoparticles via physical adsorption or an electrostatic effect. The mass fraction of the Cu/Si nanoparticles also had a significant effect on the crystalline form of PA6. The γ crystalline form of PA6 was predominant at a high mass fraction of Cu/Si to PA6. Moreover, PA6-Cu/Si with improved mechanical properties and wear resistance was generated by tuning the amount of nano-Cu/Si filler added during the polymerization. PA6-Cu/Si with a nano-Cu/Si content of 0.5% possesses the highest tensile strength and wear resistance and shows promise in applications as a functional polymer-matrix composite.     

Structural organization of plasma membrane lipids isolated from cells cultured as a monolayer and in tissue-like conditions

In this paper, folate conjugated poly(ε-caprolactone-co-4-maleate-ε-caprolactone) (P(CL-co-MCL)-folate) was prepared by a carbodiimide coupling reaction, i.e., the vitamin folic acid (FA) was covalently linked to the main chain of the maleate-functionalized polymer, poly(ε-caprolactone-co-4-maleate-ε-caprolactone) (P(CL-co-MCL)). Then the 5-Fluorouracil (5-FU) loaded nanoparticles of P(CL-co-MCL)-folate were achieved by solvent-evaporation method. Their properties were extensively studied by dynamic light scattering (DLS) and scan electron microscopy (SEM). DLS and SEM showed that the nanoparticles were in a well-defined spherical shape with a uniform size distribution. We also investigated the entrapment and in vitro release behavior, which indicated that the release speed of 5-FU could be well controlled and the release half-life period could reach 16.86h, which was 26.4 times longer than that of pure 5-FU. The in vitro targeting test displayed that the 5-FU loaded P(CL-co-MCL)-folate nanoparticles exhibited an enhanced cell inhibition because folate targeting increased the concentration of 5-FU loaded P(CL-co-MCL)-folate nanoparticles in the tumor cells with folate receptor overexpressed. Meanwhile, the tumor inhibition of 5-FU loaded P(CL-co-MCL)-folate nanoparticles was much higher than that of pure 5-FU and that of 5-FU loaded P(CL-co-MCL) nanoparticles. Therefore, P(CL-co-MCL)-folate nanoparticles would be highly beneficial for biomedical and pharmaceutical applications.     

Aggregation of sodium dodecylsulfate in aqueous nitric acid medium

Curcumin (Cur) shows low anticancer activity in vivo due to its reduced systemic bioavailability stemmed from its poor aqueous solubility and instability. Suitably functionalized nanocarriers designed to empty the drug specifically at tumor sites can potentially enhance the antitumor activity of Cur. We devised a simple method for the fabrication of water soluble Cur conjugated gold nanoparticles to target various cancer cell lines. Cur was conjugated to hyaluronic acid (HA) to get a water soluble conjugate (HA-Cur). We generated gold nanoparticles (AuNPs) by reducing chloroauric acid using HA-Cur, which played the dual role of a reducing and stabilizing agent and subsequently anchored folate conjugated PEG. These entities were probed using different analytical techniques, assayed the blood compatibility and cytotoxicity. Their interaction with cancer cell lines (HeLa cells, glyoma cells and Caco 2 cells) was followed by flow cytometry and confocal microscopy. Blood-materials interactions studies showed that the nanoparticles are highly hemocompatible. Flow cytometry and confocal microscopy results showed significant cellular uptake and internalization of the particles by cells. HA-Cur@AuNPs exhibited more cytotoxicity comparing to free Cur. The strategy, we adopted here, resulted the formation blood compatible Cur conjugated AuNPs with enhanced targeting and improved efficacy.     

Effects of nanoparticles on the flame retardancy of the ammonium sulphamate‐dipentaerythritol flame‐retardant system in polyamide 6

This paper extends the work of Lewin et al., which showed that high levels of flame retardancy could be conferred on polyamide 6 (PA6) in the presence of small concentrations of ammonium sulphamate (AS) and dipentaerythritol (DP). PA6 samples were compounded with similarly low concentrations (2.5%w/w AS and 1%w/w DP) with or without nanoclays and fumed silica present at 1 and 2%w/w levels. Compounded samples were characterized by X‐ray diffraction, thermal analysis (differential thermal analysis/thermogravimetric analysis) and Fourier transform infrared. Flammability properties were measured by UL‐94, limiting oxygen index (LOI) and cone calorimetry test methods. All PA6 blended samples with or without nanoparticles were found to be V‐2 rated which differed from the results reported by Lewin et al. for similar samples where V‐0 ratings were obtained for clay‐free samples. LOI increases promoted by the inclusion of AS and DP alone were slightly reduced following the addition of all nanoparticles with the functionalized clays showing the largest effect. Introduction of silica, however, had the smallest effect in reducing LOI. Cone calorimetric results showed that while the presence of AS and DP raise peak heat release rate values with respect to PA6, addition of nanoparticles reduced values to below that for pure PA6. These reductions are dependent on nanoparticle concentration although differences between them, within experimental error, are very similar. While smoke generation is little affected by addition of AS and DP, the presence of nanoparticles promotes a slight increase. Results were interpreted in terms of previously published mechanisms for PA6‐AS‐DP thermal degradation and nanoparticle‐polymer interactions. Copyright © 2012 John Wiley & Sons, Ltd.     

Electroanalytical Determination of Paracetamol Using Pd Nanoparticles Deposited on Carboxylated Graphene Oxide Modified Glassy Carbon Electrode

The study presents a novel paracetamol (PA) sensor based on Pd nanoparticles (PdNPs) deposited on carboxylated graphene oxide (GO?COOH) and nafion (Nf) modified glassy carbon electrode (GCE). The morphologies of the as prepared composites were characterized using high resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), and fourier transform infrared spectroscopy (FTIR). The experimental results demonstrated that Nf/GO?COOPd displayed excellent electrocatalytic response to the oxidation PA. The linear range was 0.04–800 μM for PA with limit of detection of 0.012 μM and excellent sensitivity of 232.89 μA mM^?1 cm^?2. By considering the excellent performance of Nf/GO?COOPd composite such as wider linear range, lower detection, better selectivity, repeatability, reproducibility, and storage stability, the prepared composite, especially GO?COOH support, with satisfactory electrocatalytic properties was a promising material for the modification of electrode material in electrochemical sensor and biosensor field.     

Characterization and release of triptolide-loaded poly (d,l-lactic acid) nanoparticles

Triptolide (TP), which has immunosuppressive effect, anti-neoplastic activity, anti-fertility function and severe toxicities on digestive, urogenital, blood circulatory system, was used as a model drug in this study. TP-loaded poly (d,l-lactic acid) (PLA) nanoparticles were prepared by the modified spontaneous emulsification solvent diffusion method (modified-SESD method). Dynamic light scattering system (DLS), transmission electron microscope (TEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), X-ray powder diffractometry and Fourier transform infra-red spectroscopy (FT-IR) were employed to characterize the nanoparticles fabricated for size and size distribution, surface morphology, the physical state of drug in nanoparticles, and the interaction between the drug and polymer. Encapsulation efficiency (EE) and the in vitro release of TP in nanoparticles were measured by the reverse phase high-performance liquid chromatography (RP-HPLC). The produced nanoparticles exhibited a narrow size distribution with a mean size of approximately 150 nm and polydispersity index of 0.088. The morphology of the nanoparticles exhibited a fine spherical shape with smooth surfaces without aggregation or adhesion. TP-entrapped in nanoparticles was found in the form of amorphous or semicrystalline. It was found that a weak interaction existed between the drug and polymer. In all experiments, more than 65% of EE were obtained. The in vitro release profile of TP from nanoparticles exhibited a typical biphasic release phenomenon, namely initial burst release and consequently sustained release. In this case, the particle size played an important role for the drug release. The modified-SESD method was a potential and advantage method to produce an ideal polymer nanoparticles for drug delivery system (DDS).     

A Sensitive Simultaneous Determination of Epinephrine and Piroxicam Using a Glassy Carbon Electrode Modified with a Nickel Hydroxide Nanoparticles/Multiwalled Carbon Nanotubes Composite

The electrooxidation of epinephrine (EPI) and piroxicam (PRX) has been investigated by application of nickel hydroxide nanoparticles/multiwalled carbon nanotubes composite electrode (MWCNTs‐NHNPs/GCE) using cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometry (CA) methods. The modified electrode showed suitable electrochemical responses for EPI and PRX determination. Under the optimum conditions the electrode provides a linear response versus EPI and PRX concentrations in the range of 1–220 µM and 0.7–75 µM, respectively using the DPV method. Linear responses versus EPI and PRX concentrations in the range of 1–1000 µM and 1–800 µM, respectively, were obtained using the CA method. The modified electrode was used for determination of EPI and PRX in human urine with satisfactory results.     

Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells

A magnetic nanoparticle conjugate was developed that can potentially serve both as a contrast enhancement agent in magnetic resonance imaging and as a drug carrier in controlled drug delivery, targeted at cancer diagnostics and therapeutics. The conjugate is made of iron oxide nanoparticles covalently bound with methotrexate (MTX), a chemotherapeutic drug that can target many cancer cells whose surfaces are overexpressed by folate receptors. The nanoparticles were first surface-modified with (3-aminopropyl)trimethoxysilane to form a self-assembled monolayer and subsequently conjugated with MTX through amidation between the carboxylic acid end groups on MTX and the amine groups on the particle surface. Drug release experiments demonstrated that MTX was cleaved from the nanoparticles under low pH conditions mimicking the intracellular conditions in the lysosome. Cellular viability studies in human breast cancer cells (MCF-7) and human cervical cancer cells (HeLa) further demonstrated the effectiveness of such chemical cleavage of MTX inside the target cells through the action of intracellular enzymes. The intracellular trafficking model proposed was supported through nanoparticle uptake studies which demonstrated that cells expressing the human folate receptor internalized a higher level of nanoparticles than negative control cells.     

Preparation of composite magnetic microspheres by reactive blending

A novel method for preparation of polymer-based magnetic microspheres was proposed by utilizing melt reactive blending,which was based on selective location of Fe_3O_4 nanoparticles in PA6 domains of polystyrene(PS)/polyamide 6 (PA6) immiscible blends.The morphology of PA6/Fe_3O_4 composite magnetic microspheres was studied by scanning electronic microscopy(SEM).The composite magnetic microspheres were spherical with a diameter range of 0.5-8μm;the diameter was sharply decreased with a very narrow distri...     

Preparation and characterization novel polymer-coated magnetic nanoparticles as carriers for doxorubicin

The poly(lactide-co-glycolide)-coated magnetic nanoparticles (PLGA MNPs) were prepared as carriers of doxorubicin (PLGA-DOX MNPs) through water-in-oil-in-water (W/O/W) emulsification method. The characteristics of PLGA-DOX MNPs were measured by using transmission electron microscopy (TEM) and vibrating-sampling magnetometry (VSM). It was found that the synthesized nanoparticles were spherical in shape with an average size of 100 ± 20 nm, low aggregation and good magnetic responsivity. Meanwhile, the drug content and encapsulation efficiency of nanoparticles can be achieved by varying the feed weight ratios of PLGA and DOX particles. These PLGA-DOX MNPs also demonstrated sustained release of DOX at 37 °C in buffer solution. Besides, influence of drug-loaded nanoparticles on in vitro cytotoxicity was determined by MTT assay, while cellular apoptosis was detected by Annexin V-FITC apoptosis detection kit. The results showed that PLGA-DOX MNPs retained significant antitumor activities. Therefore, PLGA-DOX MNPs might be considered a promising drug delivery system for cancer chemotherapy.