PEGylated PLGA Nanoparticles as Tumor Ecrosis Factor-α Receptor Blocking Peptide Carriers:Preparation,Characterization and Release in vitro

To assess the merits of PEGylated poly （lactic-co-glycolic acid） （PEG-PLGA） nanoparticles as drug carriers for tumor necrosis factor-α receptor blocking peptide （TNFR-BP）, PEG-PLGA copolymer, which could be used to prepare the stealth nanoparticles, was synthesized with methoxypolyethyleneglycol, DL-lactide and glycolide. The structure of PEG-PLGA was confirmed with ^1H-NMR and FT-IR spectroscopy, and the molecular weight （MW） was determined by gel permeation chromatography. Fluorescent FITC-TNFR- BP was chosen as model protein and encapsulated within PEG-PLGA nanoparticles using the double emulsion method. Atomic force microscopy and photon correlation spectroscopy were employed to characterize the stealth nanoparticles fabricated for morphology, size with polydispersity index and zeta potential. Encapsulation efficiency （EE） and the release of FITC-TNFR-BP in nanopartieles in vitro were measured by the fluorescence measurement. The stealth nanoparticles were found to have the mean diameter less than 270 nm and zeta potential less than -20 mV. In all nanoparticle formulations, more than 45% of EE were obtained. FITC-TNFR-BP release from the PEG-PLGA nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. The experimental results show that PEG-PLGA nanoparticles possess the potential to develop as drug carriers for controlled release applications of TNFR-BP.

Dual responsive block copolymer coated hollow mesoporous silica nanoparticles for glucose-mediated transcutaneous drug delivery

A self-regulated anti-diabetic drug release device mimicking pancreatic cells is highly desirable for the therapy of diabetes. Herein, a glucose-mediated dual-responsive drug delivery system, which combines pH-and H_(2)O_(2)-responsive block copolymer grafted hollow mesoporous silica nanoparticles(HMSNs)with microneedle(MN) array patch, has been developed to achieve self-regulated administration.The poly[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate]-b-poly[2-(dimethylamino)ethyl methacrylate](PPBEM-b-PDM) polymer serves as gate keeper to prevent drug release from the cavity of HMSNs at normoglycemic level. In contrast, the drug release rate is significantly enhanced upon H_(2)O_(2)and pH stimuli due to the chemical change of H_(2)O_(2)sensitive PPBEM block and acid responsive PDM block. Therefore, incorporation of anti-diabetic drug and glucose oxidase(GOx, which can oxidize glucose to gluconic acid and in-situ produce H_(2)O_(2)) into stimulus polymer coated HMSNs results in a glucose-mediated MN device after depositing the drug-loaded nanoparticles into MN array patch. Both in vitro and in vivo results show this MN device presents a glucose mediated self-regulated drug release characteristic, which possesses a rapid drug release at hyperglycemic level but retarded drug release at normoglycemic level. The result indicates that the fabricated smart drug delivery system is a good candidate for the therapy of diabetes.

Controlled Synthesis of Metal-Nanoparticles Decorated Block Copolymer Hybrid Particles via Emulsion Confined Self-assembly and Their Catalytic Applications

Comprehensive Summary Metal nanoparticles(NPs)decorated block copolymer(BCP)hybrid nanoparticles have attracted enormous attention for their actual value in catalysis,medical therapy,and bioengineering.The confined assembly of BCPs within evaporative emulsion droplet is verified as an effective method to provide polymeric scaffolds to load metal NPs.However,to date,it remains challenging to generate different types of metal NPs decorated BCP hybrid nanoparticles.Herein,we employed the emulsion confined self-assembly of poly(styrene-b-2-vinylpyridine)(PS-b-P2VP)and the followed seed-mediated growth of Au and palladium(Pd)NPs onto well-defined BCP particles to design a series of Au/Pd decorated BCP hybrid nanoparticles,which exhibited excellent catalytic activity for the reduction of 4-nitrophenol to 4-aminophenol with the reductant of NaBH4.This work may inspire more researchers to investigate the selective decoration of different metal NPs onto the polymeric scaffolds,broadening the potential applications of the inorganic/organic hybrid nanoparticles.

PEO-b-P4VP/Yttrium Hydroxide Hybrid Nanotubes as Supporter for Catalyst Gold Nanoparticles

The adsorption of poly （ethylene oxide）-b-poly（4-vinylpyridine）（PEO-b-P4VP） micelles onto the surface of yttrium hydroxide nanotubes （YNTs） resulted in the hybrid nanotubes with a dense P4VP inner layer and a stretched PEO outer layer surrounding YNTs. The dense P4VP layer was further stabilized by the crosslinking using 1,4-dibromobutane as the crosslinker. Then, the crosslinked hybrid nanotubes （CHNTs） were used as a novel nano supporter for loading the catalyst gold nanoparticles （GNPs） within the crosslinked P4VP layer. The resultant GNPs/CHNTs （GNTs loaded on CHNTs） were applied to catalyze the reduction reaction of p-nitrophenol. The results indicate that this novel nano supporter has advantages such as good dispersity in the suspension, high capacity in loading GNPs （0.87 mmol/g）, high catalytic activity of the loaded GNPs （12.9 μmol-lmin-i）, and good reusability of GNTs/CHNTs.

Temperature and anion responsive self-assembly of ionic liquid block copolymers coating gold nanoparticles

In this paper, double hydrophilic ionic liquid block copolymers （ILBCs）, poly poly[1-methyl-3-（2-methacryloyloxy propylimidazolium bromine）]-block-（N.isopro. pylacrylamide） （PMMPImB-b-PNIPAAm） was first synthesized by reversible addition- fragmentation chain transfer （RAFT） and then attached on the surface of gold nanoparticles （Au NPs） via a strong gold-sulfur bonding for preparing hybrid nanoparticles （PMMPImB-b-PNIPAAm-@-Au NPs）. The hybrid NPs had a three layers micelle-like structure, including a gold core, thermo-responsive inner shell and anion responsive outer corona. The self-assembling behavior of thermal- and anion-response from shell and corona were respectively investigated by change of temperature and addition of （CF3SO2）2N-. The results showed the hybrid NPs retained a stable dispersion beyond the lower critical solution temperature （LCST） because of the space or electrostatic protecting by outer PMMPImBo However, with increasing concentration of （CF3SO2）2N-, the micellization of self-assembling PMMPImB-b-PNIPAAm-@-Au NPs was induced to form micellar structure containing the core with hydrophobic PMMPImB- （CF3SO2）2N- surrounded by composite shell of Au NPs-PNIPAAm via the anion- responsive properties of ILBCs. These results indicated that the block copolymers protected plasmonic nanoparticles remain self-assembling properties of block copoly- mers when phase transition from outer corona polymer.

Block Copolymer Supported Gold Nanoparticles Assemblies with Exposed Gold Surface

Polymer-involved nanoparticles or nanoparticle assemblies are now facing a crossroad,where the exposure of nanoparticle and multiple nanoparticles cannot be obtained at the same time.Therefore,a new series of nanoparticle clusters is synthesized,where multiple gold nanoparticles assemble with amphiphilic block copolymers supporting inside.The exposure of gold nanoparticles of the structure is confirmed and increases the reduction rate of 4-nitrophenol by 60%.The assemblies can also be used as surface enhanced Raman scattering(SERS)probes with an enhancement factor(EF)as high as 3×10^(3).

A new drug carrier:Magnetite nanoparticles coated with amphiphilic block copolymer

This paper reports on the synthesis and characterization of 4 nm magnetite nanoparticles coated with amphiphilic block copolymers of poly(ethyl methacrylate)-b-poly(2-hydroxyethyl methacrylate) (PEMA- b-PHEMA) by surface-initiated atom transfer radical polymerization (ATRP), which can act as new potential carriers for hydrophobic targeted drug delivery. Vibrating sample magnetometer analysis indi-cated that the magnetite nanoparticles were superparamagnetic at room temperature. Thermogravim-etric analysis (TGA) was applied to studying the property of surface of magnetite nanoparticles, and the surface density of macromolecules was calculated. The grafting density of oleic acid, BrMPA and PEMA was 5.8, 3.9, 0.16 chain/nm2 respectively, which indicates that the initiation efficiency decreases due to the influence of large space of oleic acid molecules. In vitro progesterone and (-)-isoproterenol hy-drochloride release in phosphate buffered saline (PBS) at pH 7.0 and 37℃ was conducted in order to demonstrate the function of drug loading and release. The results showed that the amount of drug carried into the core-shell Fe3O4@PEMA-b-PHEMA depends on the length of hydrophobic segment of block copolymer. The release of progesterone (37% after 22 h in our previous work) was compared with the release of (-)-isoproterenol hydrochloride (80% after 50 min), demonstrating that the strong hy-drophobic interaction between hydrophobic segment and drug can effectively control the release of hydrophobic drugs.

嵌段共聚物与接枝纳米粒子在硬受限下的自组装

采用自洽场方法(SCFT),研究了两嵌段共聚物与接枝均聚物纳米粒子在硬受限下的自组装行为,详细探讨了板的性质与受限程度对体系相行为的影响,结果发现随着受限程度和板性质的变化,体系发生了多次结构转变.当AB两嵌段共聚物对称(f_(a)=f_(b)=0.5)时,在体系受限较小(70≤N2≤120)情况下,无论板的性质如何变化,体系均会形成波浪层状和平行层状混合结构.当受限程度增大(40≤N2≤60)时,在中性板中,体系会自组装形成同心圆环结构;在A吸引板中,体系会形成柱状结构和平行层状混合结构;在B吸引板中,体系会自组装形成带状、层状以及同心圆环混合结构.当受限程度较大(20≤N2≤30)时,在中性板和A吸引板中,体系最终转变为垂直层状结构;在B吸引板中,体系自组装形成平行层状结构.最后,还探讨了熵效应对体系结构形成的影响.

Tailores Design and Characterization of Peroxide-containing Linear, Blick and Highly Branched Oligoelectrolytes and Derived Functional Nanoparticles with Special Properties

1 Results The development of novel surface-active block, comb-like and branched copolymers with peroxide-containing chains as well as derived functional luminescent and magnetic nanoparticles are the objectives of presented study. Main experimental approaches based on tailored synthesis of the oligoperoxide surfactants of desired structures and derived coordinating complexes of transitional and rare earth elements are developed. Functional oligoperoxide based possibilities of the synthesis of luminescen...

Transport of citrate and polymer coated gold nanoparticles(AuNPs) in porous media:Effect of surface property and Darcy velocity

With the release of nanoparticles(NPs)into the subsurface,it is imperative to better understand the fate and transport of NPs in porous media.Three types of stable AuNPs were used as model NPs to investigate the impact of surface coatings(type and coverage)and water velocity on the NP transport in a porous media(column studies).The NPs were electrostatic stabilized citrate AuNPs and sterically stabilized AuNPs with amphiphilic block co-polymer(PVA-COOH)in two particle/polymer ratios(weak vs.strong stabilization).The citrate AuNPs transport was sensitive to ionic changes in the mixing front of the plume,where destabilization occurred,and will therefore depend on the size/type of release.Blocking of deposition sites by aggregates was seen to facilitate transport,whereby a higher flow velocity(larger shadow zone)also resulted in better transport.The polymeric surface coating had great impact with steric repulsion as a main force contributing to the transport of NPs in the porous media.Sufficient polymer coating was crucial to obtain highly unfavorable attachment conditions(very lowα)where the enhanced NP mobility was independent of the water velocity(comparable to solute tracer).Without sufficient steric stabilization,the transport and recovery was significantly reduced compared to the solute tracer,but increased with increasing water velocity.This highlights the importance of sufficient surface coating to achieve enhanced mobility,but also the increased risk of spreading to down-gradient receptors.For the(weakly)sterically stabilized NPs,the loss of polymer through ligand exchange with the porous media negates transport.

温敏性嵌段共聚物PNIPAM-b-PEO修饰的纳米金的制备及其表征

通过三硫酯基团与金的相互作用,将结点处带有三硫酯基团的嵌段共聚物聚异丙基丙烯酰胺-聚氧化乙烯(PNIPAM-b-PEO)接枝到纳米金的表面制备得到温敏性纳米金颗粒。制备得到的V型聚合物刷修饰的纳米金(Au-V聚合物刷)经溶解度测试、紫外(UV–vis)、红外(FT-IR)、透射电镜(TEM)和光散射(DLS)测试,结果发现Au-V聚合物刷可以溶解在水中也可以溶解在有机溶剂中。Au-V聚合物刷表现出温敏性,温度高于34℃时表现出一定程度的聚集。

PEG-PLGA嵌段共聚物空白纳米粒的冻干工艺筛选

研究采用外观、色泽、再分散性、胶体性、粒径变化及其粒度分布作为指标综合评定,考察PEG-PLGA嵌段共聚物纳米粒冷冻干燥工艺,并研究工艺中冻干保护剂的使用对冻干效果的影响,筛选出适合的冻干方法.实验结果表明,采用麦芽糖作为冻干保护剂,并在浓度为4%条件下所制备得到的纳米粒质量较优良,复水合后采用激光粒度仪测定粒径大小及其分布,平均粒径为255.5±55nm,PDI范围为0.221±0.085.上述实验结果提示,PEG-PLGA空白纳米粒冷冻干燥工艺可以成功制备出质量稳定的冻干纳米粒,为进一步载药研究奠定基础.

胰岛素聚酯纳米粒的制备及药效学研究

:目的 探讨ε 己内酯 D ,L 丙交酯嵌段共聚物纳米粒 (PCLA NP)作为新型药物载体的可能性。方法 采用双乳化溶媒蒸发法制备了胰岛素嵌段共聚物纳米粒 (INS PCLA NP) ,透射电镜考察其形态 ;HPLC测定胰岛素的包封率 ,并考察了影响纳米粒粒径及包封率的各种因素 ;应用抗体捕捉实验验证纳米粒的载药机制 ;考察INS PCLA NP的体外释药特性 ;建立了糖尿病大鼠模型 ,通过葡萄糖氧化酶法 (GOD PAP)测定血糖浓度来评价INS PCLA NP经皮注后的降血糖作用 ,并计算INS PCLA NP的药理生物利用度 (pharmacologicalbioavailability ,PBA)。结果 INS PCLA NP的平均粒径为 16 7.3nm ;纳米粒的平均包封率为 37.79 % ;PVA浓度和超声时间对粒径及包封率影响显著 ;抗体捕捉实验证实被包封的胰岛素大部分 (约 5 3 % )存在于纳米粒的表面 ;INS PCLA NP的体外释药曲线分为两相 :突释释药相和缓释平台相 ;药效学研究表明 ,12u·kg-1的INS PCLA NP经皮下给药后即有明显的降血糖作用 ,药理生物利用度为 74.76 %。结论 PCLA

陶瓷先驱体Polyvinylsilazane-b-Polystyrene的合成及纳米陶瓷颗粒的制备

以DTBA为链转移剂,VSZ和苯乙烯为单体,通过可逆加成断裂链转移(RAFT)聚合合成了嵌段共聚物陶瓷先驱体Polyvinylsilazane-b-Polystyrene(PVSZ-b-PS)。利用DLS、TEM、AFM等技术,考察了PVSZ-b-PS在选择性溶剂DMF中自组装成胶束的行为。结果表明,胶束为核-壳结构的球形,其中PVSZ为核、PS为壳,胶束直径70～110nm。PVSZ-b-PS胶束制成的聚合物膜能完整保留胶束的球形特征,800℃热解能制得直径为30～40 nm的纳米陶瓷颗粒。XRD结果表明陶瓷颗粒是SiC结晶相。

嵌段聚合物修饰的金纳米粒子的制备及表征

通过RAFT合成聚(甲基丙烯酸缩水甘油酯)-b-聚(乙二醇甲基丙烯酸酯)嵌段共聚物(PGMA-bPMAPEG),再用半胱氨酸(Cys)使PGMA中的环氧基团开环,制备含有巯基的两亲水嵌段聚合物PMAPEG-bP(GMA-Cys)。并以其作为修饰剂,通过原位还原法使HAuCl4在NaBH4的还原下制备金/聚合物纳米复合粒子(Au@PMAPEG-b-P(GMA-Cys)NPs)。经FT-IR、UV-vis、TG、XRD、TEM和DLS表征,发现金纳米复合粒子呈均匀分散的球形,平均粒径约为10nm,在527nm处出现了金纳米粒子的表面等离子共振吸收峰,金约占总重量的49%。由于外层嵌段共聚物的修饰作用,金纳米复合粒子在室温下放置6个月未发生粒子间的聚集。

聚天冬氨酸苄酯修饰的泊洛沙姆纳米粒制备和表征

通过泊洛沙姆188引发L-天冬氨酸-β-苄酯-N-羧酸酐（BLA-NCA）开环聚合,合成一种新型的药物载体材料PBLA-POLO-PBLA嵌段共聚物。利用核磁共振（^1HNMR）、傅里叶变换红外光谱法（FTIR）和凝胶渗透色谱（GPC）对合成的聚合物结构和分子量进行表征;运用CCK-8法研究了聚合物材料对A549的细胞毒性。采用乳化溶剂蒸发法制备伐昔洛韦（VACV）聚合物纳米粒并对其理化性质进行了研究。动态光散射粒度仪（DLS）和透射电子显微镜（TEM）结果表明,该载药纳米粒的尺寸为200 nm左右,具有圆球形态并且分散性能良好。用高效液相色谱法测得其载药量为4.36%,以透析法观察到载药纳米粒在磷酸缓释溶液中96 h时释放达到70.22%,具有明显缓释作用。因此,PBLA-POLO-PBLA嵌段共聚物在纳米载药系统中作为药物载体有着良好的应用前景。

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。

掺杂无机性纳米粒子的嵌段聚合物体系的场理论模拟研究

自洽场理论(SCFT)是目前国内外研究纳米粒子聚合物复合材料以及聚合物材料的重要研究理论之一,基于自洽场理论对掺杂有无机性纳米粒子的AB嵌段聚合物体系进行场理论自组装模拟。对无机性纳米粒子AB嵌段聚合物体系中的纳米粒子与AB嵌段聚合物之间的相互作用势,本文引入一个势函数u(r),然后对体系进行自洽场理论分析和计算模拟。通过对纳米粒子半径、浓度对体系平衡态影响的计算模拟研究发现:当纳米粒子浓度、半径逐步增大时,其纳米粒子表面与聚合物的分布方式从层状式分布逐步过渡到发散式分布;同时还研究发现无机性纳米粒子嵌段聚合物体系中的A、B嵌段聚合物浓度对纳米粒子的分布情况无影响。综述以上的结果验证无机性纳米粒子/嵌段聚合物体系中纳米粒子的表面效应和体积效应对体系的平衡态有很大的影响。

海藻多糖基嵌段共聚物/纳米金复合物的制备

目的：原位法制备海藻多糖基聚乙烯基吡咯烷酮嵌段共聚物/纳米金复合物（ SA-330-S2-Au）。方法首先合成改性海藻多糖基二硫代酯,并用作RAFT聚合的链转移剂（CTA）,制备海藻多糖基聚乙烯基吡咯烷酮嵌段的共聚物（ SA-330-S2）,然后利用SA-330-S2自组装特性,原位法制备SA-330-S2-Au,并用FT-IR、NMR、DSC、TEM、SEM等方法进行分析表征。结果复合物SA-330-S2-Au中的纳米金粒子大小约10~30 nm,湿态时纳米复合纳米粒子的平均粒径约为54.4 nm,由于复合纳米粒子外壳层的海藻多糖基嵌段共聚物的稳定化作用,SA-330-S2-Au水溶液储存期超过6个月,且有明显荧光。结论 SA-330-S2-Au水溶液稳定且具有荧光特性,有望应用于肿瘤诊疗领域。

两水亲性嵌段共聚物修饰Fe_3O_4磁纳米粒子的一步合成及性能表征

采用可逆加成-断裂链转移（RAFT）聚合,合成了两水亲性嵌段共聚物聚（4乙烯基吡啶）-b-聚（甲基丙烯酸聚乙二醇酯）（P4VP-b-PMAPEG）和聚（丙烯酸）-b-聚（甲基丙烯酸聚乙二醇酯）（PAA-b-PMAPEG）,通过多元醇还原法制备了两水亲性嵌段共聚物修饰的Fe3O4 磁纳米粒子.并利用红外光谱（FT-IR）、X射线粉末衍射（XRD）、透射电镜（TEM）对磁纳米粒子进行表征.结果表明,嵌段共聚物修饰的Fe3O4 磁纳米粒子为大小均匀的球状颗粒,其粒径在10~20nm.振动样品磁强计测试结果显示,在室温、外加磁场下,经PAA-b-PMAPEG 及P4VP-b-PMAPEG修饰的Fe3O4 磁纳米粒子的饱和磁化强度分别为63.1A·m2/kg和50.2A·m2/kg,该磁纳米粒子均呈现超顺磁性.