Polymeric nanoparticles of poly(2-oxazoline), tannic acid and doxorubicin for controlled release and cancer treatment

A straightforward coassembly strategy was developed for the preparation of polymeric nanoparticles driving by the intermolecular hydrogen bond between neutral poly(2-methyl-2-oxaozline)(PMeOx),tannic acid(TA) and doxorubicin hydrochloride(Dox).The occurrence of the hydrogen-bonding amongst the different functionalities within the formed nanoparticles was verified by infrared(IR) spectroscopy.Scanning electron microscopy(SEM),dynamic light scattering(DLS),UV-vis absorption and photoluminescent measurements indicated the rapid formation of uniform and water dispersible/stable nanoparticles.The relative poor stability of PMeOx-TA-Dox in fetal bovine serum(FBS) solution enabled the rapid separation of Dox and PMeOx-TA,facilitating the release of Dox and its entrance into cellular nuclei as revealed by confocal laser scanning microscopy(CLSM).The presented strategy may provide an efficient alternative for the construction of multifunctional nanomedicines.     

Preparation and characterization of N-succinyl-N'-octyl chitosan micelles as doxorubicin carriers for effective anti-tumor activity

N-Succinyl-N′-octyl chitosan (SOC) was prepared and characterized by elemental analysis, FTIR, ¹H NMR, WAXD and TG. An anticancer drug, doxorubicin (DOX), was incorporated into polymeric micelles forming by SOC in aqueous solutions. Critical micelle concentrations (CMC) of SOC were determined by fluorescence spectroscopy. The DOX-loaded SOC micelles were characterized by measurement of size and drug loading. The loading content of DOX increased with increasing drug-to-carrier ratio, and the more amount of the octyl chain, the higher the drug loading content. The average size, which was affected by the amount of octyl chain and drug loading content, was in the range of 100–200 nm. The polymeric micelles containing doxorubicin in the core region exhibited a sustained release and more cytotoxic activity against HepG2, A549, BGC and K562 than doxorubicin alone, this can be attributed to an endocytosis mechanism rather than passive diffusion.     

Preparation and characterization of poly(acrylic acid)-based nanoparticles

The present investigation describes the synthesis and characterization of nanoparticles based on poly(acrylic acid) (PAA) intramolecularly cross-linked with diamine, 2,2′-(ethylenedioxy)bis(ethylamine), using water-soluble carbodiimide. The aqueous colloid dispersions of nanoparticles were clear or mildly opalescent depending on the ratio of cross-linking, pH of the solution, and the molecular weight of PAA, finding consistent with values of transmittance between 3% and 99%. The structure was determined by nuclear magnetic resonance spectroscopy, and the particle size was identified by dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. It was found that particle size depends on the pH, and at a given pH, it was caused by the ratio of cross-linking and the molecular weight of PAA. Particle size measured by TEM varied in the range of 20 and 80 nm. In the swollen state, the average size of the particles measured by DLS was in the range of 35–160 nm.     

纳米银/二甲基砜/聚乳酸-乙醇酸静电纺丝人工敷料的制备及生物评价

采用静电纺丝方法制备了纳米银(n-Ag)/二甲基砜(MSM)/聚乳酸-乙醇酸(PLGA)抗菌人工敷料. 通过场发射扫描电子显微镜(ESEM)和能量离散X射线光谱(EDX)研究敷料的微观结构及表面元素组成. 同时对敷料的力学性能、 吸水性、 细胞相容性及抗菌性进行测试, 结果表明, 该敷料内部纤维呈交叉的网格状结构, 互相连结, 随着n-Ag含量的增加, 纤维的力学强度逐渐增大, 吸水性能逐渐增强. 当n-Ag质量分数达到1%以上时, 敷料对革兰氏阳性菌金黄色葡萄球菌和革兰氏阴性大肠杆菌具有良好的抗菌活性. 细胞实验结果表明, 当n-Ag含量在0.01%～10%之间时, 敷料属无毒性或低毒性; 当其含量小于1%时, 有助于细胞的生长和增殖. 因此, 该敷料具有良好的细胞相容性和抗菌性能.     

Development of novel magnetic nano-carriers for high-performance affinity purification

We developed novel magnetic nano-carriers around 180 nm in diameter for affinity purification. Prepared magnetic nano-carriers possessed uniform core/shell/shell nano-structure composed of 40 nm magnetite particles/poly(styrene-co-glycidyl methacrylate (GMA))/polyGMA, which was constructed by admicellar polymerization. By utilizing relatively large 40 nm magnetite particles with large magnetization, the magnetic nano-carriers could show good response to permanent magnet. Thanks to uniform polymer shell with high physical/chemical stability, the magnetic nano-carriers could disperse in a wide range of organic solvent without disruption of core/shell structure and could immobilize various kinds of drugs. We examined affinity purification using our prepared magnetic nano-carriers with anti-cancer agent methotrexate (MTX) as ligand. Our magnetic nano-carriers showed higher performance compared to commercially available magnetic beads in terms of purification efficiency of target including extent of non-specific binding protein.     

共同装载吴茱萸碱和Fe3O4纳米粒子的磁性药物载体的制备

以单甲醚-聚乙二醇-聚（丙交酯-乙交酯）（mPEG-PLGA）作为载体,采用溶液透析的方法共同装载抗癌药物吴茱萸碱和Fe₃O₄ 磁性纳米粒子. 通过透射电子显微镜、红外光谱、紫外-可见光谱及体外释放实验、普鲁士蓝染色、体外毒性实验和磁靶向研究,综合评价了磁性纳米药物载体的性能. 结果表明,磁性药物载体胶束分散性良好,粒径均一,有较高的载药量和包封率,能够实现药物缓释,具有磁靶向特性.     

n-Ag/AD/PLGA功能性材料的制备及生物学性能

利用静电纺丝技术制备了纳米银(n-Ag)/山莨菪碱(AD)/聚乳酸-乙醇酸(PLGA)功能性材料.通过场发射扫描电子显微镜(ESEM)和傅里叶变换红外光谱(FTIR)研究了材料的微观结构及组成,评价了材料的体外药物释放、抑菌性、细胞相容性及细胞毒性.FTIR结果表明,山莨菪碱已担载到n-Ag/AD/PLGA材料中,且随着山莨菪碱含量的增加,n-Ag/AD/PLGA材料内纤维的平均直径逐渐增大.药物释放试验结果证明,山莨菪碱可以逐渐释放.当山莨菪碱的质量分数为1%~5%时,n-Ag/AD/PLGA材料无毒性,且有助于小鼠L929成纤维细胞的生长和增殖.研究结果表明,n-Ag/AD/PLGA材料具有良好的抗菌性能和细胞相容性,担载的山莨菪碱可有效释放,为糖尿病足部感染的临床治疗提供新的人工敷料.     

Effects of the Molecular Weight of PLGA on Degradation and Drug Release In vitro from an mPEG-PLGA Nanocarrier

We successfully synthesized four kinds of copolymers with varying molecular weights of poly(lactide-co-glycolide)(PLGA) to yield methoxy-poly(ethylene glycol)-block-poly(lactide-co-glycolide)(mPEG-PLGA) nanocarriers:mPEG-PLGA(3k), mPEG-PLGA(9k), mPEG-PLGA(11k) and mPEG-PLGA(16k). An antitumor drug, 10-hydroxycamptothecin(HCPT), was encapsulated into the mPEG-PLGA nanocarrier cores by self-assembly in dialysis. The lower molecular weight nanocarriers degraded more quickly, resulting in mass loss, pH decline, and a rapid HCPT release rate in vitro. The degradation and drug release of the nanocarriers were dependent on the PLGA molecular weight. However, the larger molecular weight nanocarriers could not increase the loading content and encapsulation efficiency. Considering the antitumor effect of these nanocarriers, the mPEG-PLGA(9k) nanocarrier, which had the highest drug loading content[(7.72±0.57)%] and a relatively high encapsulation efficiency[(22.71±5.53)%], is an optimum agent for drug delivery.     

肾上腺髓质素微球复合PLGA/纳米羟基磷灰石支架材料的制备及生物活性评价

利用离子乳化交联法制备了负载肾上腺髓质素的壳聚糖微球,应用热致相分离法制备了乳酸和乙醇酸共聚物/纳米羟基磷灰石(PLGA/nHA)支架材料并在其中包覆载药微球.通过扫描电子显微镜、体外释放行为、材料溶血行为、碱性磷酸酶(ALP)活性的测定、支架材料表面细胞荧光染色和MTT[3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐]比色法等手段综合评价载药支架材料的性能及生物活性.结果表明,微球直径均匀,载药支架孔径大小合适并相互穿通.支架材料的溶血率小于5%,符合医用材料的溶血实验要求.载药支架及支架材料本身对成骨细胞及血管内皮细胞的增殖以及成骨细胞的分化均有一定的促进作用.     

Synthesis and characterization of novel amphiphilic copolymer stearic acid-coupled F127 nanoparticles for nano-technology based drug delivery system

Pluronic, F127, amphiphilic block copolymers, are used for several applications, including drug delivery systems. The critical micelle concentration (CMC) of F127 is about 0.26-0.8 wt% so that the utility of F127 in nano-technology based drug delivery system is limited since the nano-sized micelles could dissociate upon dilution. Herein, stearic acid (SA) was simply coupled to F127 between the carboxyl group of SA and the hydroxyl group of F127, which formed a novel copolymer named as SA-coupled F127, with significantly lower CMC. Above the CMC 6.9 × 10(-5)wt%, SA-coupled F127 self-assembled stable nanoparticles with Zeta potential -36 mV. Doxorubicin (DOX)-loaded nanoparticles were made, with drug loading (DL) 5.7 wt% and Zeta potential -36 to -39 mV, and the nanoparticles exhibited distinct shape with the size distribution from 20 to 50 nm. DOX-loaded nanoparticles were relatively stable and exhibited DOX dependant cytotoxicity toward MCF-7 cells in vitro. These results suggest that SA-coupled F127 potentially could be applied as a nano-technology based drug delivery method.     

Chitosan-coated magnetic nanoparticles as carriers of 5-Fluorouracil: Preparation,characterization and cytotoxicity studies

The chitosan-coated magnetic nanoparticles (CS MNPs) were prepared as carriers of 5-Fluorouracil (CS–5-Fu MNPs) through a reverse microemulsion method. The characteristics of CS–5-Fu MNPs were determined by using transmission electron microscopy (TEM), FTIR spectroscopy and vibrating-sampling magnetometry (VSM). It was found that the synthesized CS–5-Fu MNPs were spherical in shape with an average size of 100 ± 20 nm, low aggregation and good magnetic responsivity. Meanwhile, the drug content and encapsulation rate of the nanoparticles was 16–23% and 60–92%, respectively. These CS–5-Fu MNPs also demonstrated sustained release of 5-Fu at 37 °C in different buffer solutions. The cytotoxicity of CS–5-Fu MNPs towards K562 cancer cells was investigated. The result showed that CS–5-Fu MNPs retained significant antitumor activities. Additionally, it was observed that the FITC-labeled CS–5-Fu MNPs could effectively enter into the SPCA-1 cancer cells and induced cell apoptosis.     

Synthesis and characterization of poly(d,l-lactide-co-glycolide) modified by maleic anhydride and 1,4-butanediamine

Bone tissue engineering is sought to apply strategies for bone defects healing biodegradable porous scaffolds without limitations and shortcomings. In this work, we have developed a novel maleic anhydride (MAH) and 1,4-butanediamine modified poly(lactide-co-glycolide) polymer (BMPLGA). The synthesized polymer was characterized by Fourier transform infrared spectrometry (FTIR), Nuclear magnetic resonance spectra (¹H NMR), gel permeation chromatography (GPC) and contact angle measurements. In addition, cell morphologies in the extracts and cell cytotoxity were also studied. The results showed that the BMPLGA was successfully obtained by introducing MAH and 1,4-butanediamine into PLGA in bulk. The introduction of anhydride and amino groups improved the hydrophilicity of PLGA. Fibroblastic cells showed normal morphologies in BMPLGA extracts, and the BMPLGA materials showed no cell cytotoxicity. The synthetic BMPLGA material may have potentials for biomedical applications due to improving hydrophilicity.     

A novel optical thrombin aptasensor based on magnetic nanoparticles and split DNAzyme

In this paper, we report a novel and sensitive optical sensing protocol for thrombin detection based on magnetic nanoparticles (MNPs) and thrombin aptamer, employing split HRP-mimicking DNAzyme halves as its sensing element, which can catalyze the H₂O₂-mediated oxidation of the colorless ABTS into a blue-green product. A single nucleotide containing the recognition element and sensing element is utilized in our protocol. The specific recognition of thrombin and its aptamer leads to the structure deformation of the DNA strands and causes the split of the DNAzyme halves. Therefore, the decrease of absorption spectra can be recorded by the UV–visible Spectrophotometer. DNA-coated MNPs are utilized to separate the interferential materials from the analyst, thus making this assay can be applied in the detection of thrombin in complex samples, such as human plasma. This original, sensitive and cost-effective assay showed favorable recognition for thrombin. The absorbance signals with the concentration of thrombin over a range from 0.5 to 20 nM and the detection limit of thrombin was 0.5 nM. The controlled experiments showed that thrombin signal was not interfered in the presence of other co-existence proteins.     

Preparation, characterization and surface study of poly-epsilon caprolactone magnetic microparticles

Magnetic microparticles (MMP) have shown to be applied in increasing applications in various fields of biotechnology and medicine. One of their most promising utilization is the magnetic resonance imaging (MRI) in which superparamagnetic substances as magnetite are used in a nanometric size (less than 30 nm) and encapsulated within locally injected biodegradable microparticles. In this paper, magnetite has been encapsulated in polymer-based microparticles. The MMP have been prepared by an emulsion evaporation method. The different parameters influencing the particles size were investigated. The size was found to decrease as the stirring speed or the stabilizer amount (to certain limit) increases. The encapsulation efficacy was more than 90% yielding a magnetite loading of up to 30%, w/w. The X-ray photoelectron spectroscopy (XPS) showed less than 2% of iron atoms at the microparticles surface. The zeta potential response of MMP towards pH variation was very similar to that of magnetite-free microparticles confirming the encapsulation of magnetite within the microparticles. X-ray diffraction assays showed that magnetite crystalline structure was conserved after emulsification and MMP formation. Vibration simple magnetometer (VSM) showed a superparamagnetic profile of the MMP with a magnetic saturation increasing with the increased magnetite amount in the microparticles. These magnetic microparticles can enable clinicians to control microparticles distribution after a local administration in tumors by MRI. They can also be administered to target a defined tumor area by focusing a magnetic field on the surfaces covering the cancerous tissue.     

Design, synthesis and characterization of novel biodegradable macrodiols based on poly（DL-lactic acid） and poly（p-dioxanone）

Integrating poly(lactic acid)(PLA),glycolic acid(GA) and ethylene glycol(EG) will hopefully result in a novel copolymer that combines such advantages as fastened and controllable release rate and improved flexibility together with good biocompatibility.In this study,p-dioxanone(PDO) was employed to copolymerize with DL-lactide(LA) via ring-opening melt polymerization using Sn(Oct)_2 as an initiator and ethylene glycol as a co-initiator.The obtained degradable macrodiols(HO-P(LA-co-PDO)-OH) were just such...     

具有磁效应的温敏性药物载体的制备及表征

在合成具备一定分子结构的聚(N-异丙基丙烯酰胺)-聚乳酸(PNIPAAm-PLA)嵌段共聚物的基础上,采用透析法制备了PNIPAAm-PLA共聚物磁性复合胶束和囊泡。本文发现不同的制备工艺条件会分别形成胶束和囊泡两种载体形态,并对两种载体的形貌进行了细致对比,发现两种结构特点的载体分别适合疏水性和亲水性药物的装载。对复合胶束的最低临界溶解温度(LCST)进行了表征研究,得到其LCST在38℃左右,略高于人体体温。对不同Fe4O3磁性粒子投料比对应制备的复合胶束的磁性能进行了较详细的测试,发现磁性粒子的加入量对其磁响应性影响不大。     

Synthesis and characterization of magnetic nanoparticles

Magnetic nanoparticles with average diameter in the range of 6.4-8.3 nni have been synthesized by a chemical co-precipitation of Fe(Ⅱ)and Fe(Ⅲ)salts in 1.5 M NH4OH solution.The size of the magnetic particles is dependent on both temperature and the ionic strength of the iron ion solutions.The magnetic particles formed at higher temperature or lower ionic strength were slightly larger than those formed at lower temperature or higher ionic strength respectively.In spite of the different reaction conditions,all the resultant nanoparticles are nearly spherical and have a similar crystalline structure.At 300 K,such prepared nanoparticles are superparam-agnetic.The saturation magnetizations for 7.8 and 6.4 nm particles are 71 and 63 emu/g respectively,which are only ~ 20-30% less than the saturation magnetization(90 emu/g)of bulk Fe3O4 Our results indicated that a control of the reaction conditions could be used to tailor the size of magnetic nanoparticles in free precipitation.     

改性纳米羟基磷灰石/PLGA复合材料的制备及生物活性

以低聚乳酸接枝改性的羟基磷灰石纳米粒子(op-HA)和聚丙交酯-乙交酯(PLGA)制备的生物可降解纳米复合材料(op-HA/PLGA)为研究对象, 采用FTIR, TGA, ESEM和EDX分析其接枝反应、接枝率、表面形貌和钙磷沉积情况, 通过在材料膜表面接种兔成骨细胞进行体外培养, 采用荧光染色、NIH Image J图像分析和Real-time PCR综合评价细胞在材料表面的形态、黏附面积比、增殖能力和基因表达水平, 以此评价新型骨修复纳米复合材料op-HA/PLGA的表面性质和生物活性. 研究结果表明, op-HA的表面接枝率为8.3%, 掺入至PLGA后可形成富含钙磷的粗糙表面, 促进成骨细胞的黏附、扩展和增殖, 提高Ⅰ型胶原蛋白(Collagen-Ⅰ)、骨形态蛋白-2(BMP-2)和骨连接蛋白(Osteonectin)的基因表达水平, 提高材料的钙磷沉积能力. op-HA/PLGA具有良好的细胞相容性和成骨活性.     

Synthesis,characterization, and biological evaluation of doxorubicin containing silk fibroin micro- and nanoparticles

The aim of this study was biological evaluation of doxorubicin containing silk fibroin micro- and nanoparticles (Dox-MF and Dox-NF). Dox-MF and Dox-NF were synthesized. Cell toxicity on MCF-7, Saos2, and HFF cells was assessed using MTT assay. Induced apoptosis was assessed using flow cytometry and staining with PI/annexin V. Production of reactive oxygen species (ROS) was measured. Gene expression of p53 was evaluated by real-time PCR. FTIR, SEM, and DLS confirmed the accurate synthesis. Cytotoxicity of Dox-MF and Dox-NF showed significant inhibition of cell growth compared with the controls. Regarding Dox-NF, a significant increase was seen in mRNA level of P53 in MCF-7 and SAOS-2 ​cells and a significant decrease in HFF cells compared to the controls. There was a significantly higher expression of P53 gene in MCF-7 and HFF cells treated by Dox-MF. However, a significant decrease in P53 gene expression was detected in SAOS-2 ​cells. Significant apoptotic induction of cell lines by Dox-MF and Dox-NF was observed in both early and late stages. Dox-MF and Dox-NF acted in the direction of cell death through the apoptotic pathway and changing p53 gene expression. So, Dox-MF and Dox-NF can be considered as a candidate for new anticancer agents.     

Synthesis and characterization of heterocyclic functionalized polymers by click reaction: Preparation of magnetic nanocomposites and studies on their thermal,mechanical, photophysical and metal ions removal properties

This work reports synthesis and characterization of heterocyclic functionalized polymers, poly(triazole-etherimidazole)s(PTAEI), from a dialkyne-terminated compound, 3-(4,5-bis(4-(propargyloxy)phenyl)-1H-imidazol-2-yl)-9-ethyl-9H-carbazole, by using click reaction. PTAEIs were characterized and their properties such as solubility, thermal, mechanical, photophysical and metal ions adsorption were investigated. These polymers had weight average molar masses(Mw) in the range of 19100-26700 g/mol, exhibited excellent solubility in polar aprotic solvents and formed low-colored flexible thin films by solution casting method. They exhibited good thermal stability with glass transition temperatures(Tg) between 160 °C and 211 °C and 10% weight loss temperatures(T10%) in the range of 308-426 °C. Nanocomposites of PTAEIs with epoxide-terminated Fe3O4 showed that strong interfacial interaction between inorganic particles and the polymer matrix contributed to the enhanced thermal and mechanical properties. The photoluminescence intensity of the PTAEIs increased and the spectra red shifted with increasing Fe3O4 content. The PTAEIs and nanocomposites were tested for their extraction capability of metal ions from aqueous solutions either individually or in the mixture.