MULTI-WALL CARBON NANOTUBE-BASED DNA NANOSENSOR FOR DETERMINING MITOXANTRONE-DNA INTERACTION IN-VITRO

The present study involves the development of a carbon nanotube based DNA nanosensor to determine the toxicological behavior of mitoxantrone (MTX). Mitoxantrone intercalates with DNA and produces a MTX-DNA adduct, resulting in the blockade of protein synthesis and excessive production of free radicals in the myocardium which eventually leads to cardiac toxicity. So, our work employs a DNA nanosensor to investigate the interaction of MTX with DNA. Multi-wall carbon nanotubes (MWCNTs) were functionalized with carboxyl group and were used for immobilization of DNA to construct the DNA nanosensor. The DNA nanosensor was immersed in MTX solution to monitor MTX-DNA interaction with respect to time and alter the resistance of the nanosensor. It was observed that MTX-DNA interaction is fast initially and as time elapses, the change in interaction gets slow due to formation of MTX-DNA adduct. The limit of detection (LOD) and limit of quantification (LOQ) were found as 150 (ng/mL) and 456 (ng/mL), respectively, for DNA nanosensor. This study suggests that the potentiometric nanosensor allows real-time monitoring of the drug-DNA interaction changes by measuring the potential at DNA/sensor interface which can prove to be an important tool in drug discovery pipelines and molecular toxicology.     

Dendrimer as nanocarrier for drug delivery

Dendrimers are novel three dimensional, hyperbranched globular nanopolymeric architectures. Attractive features like nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery and cavities in the interior distinguish them amongst the available polymers. Applications of dendrimers in a large variety of fields have been explored. Drug delivery scientists are especially enthusiastic about possible utility of dendrimers as drug delivery tool. Terminal functionalities provide a platform for conjugation of the drug and targeting moieties. In addition, these peripheral functional groups can be employed to tailor-make the properties of dendrimers, enhancing their versatility. The present review highlights the contribution of dendrimers in the field of nanotechnology with intent to aid the researchers in exploring dendrimers in the field of drug delivery.     

Ganciclovir and Its Hemocompatible More Lipophilic Derivative Can Enhance the Apoptotic Effects of Methotrexate by Inhibiting Breast Cancer Resistance Protein (BCRP)

Efflux transporters, namely ATP-binding cassette (ABC), are one of the primary reasons for cancer chemoresistance and the clinical failure of chemotherapy. Ganciclovir (GCV) is an antiviral agent used in herpes simplex virus thymidine kinase (HSV-TK) gene therapy. In this therapy, HSV-TK gene is delivered together with GCV into cancer cells to activate the phosphorylation process of GCV to active GCV-triphosphate, a DNA polymerase inhibitor. However, GCV interacts with efflux transporters that are responsible for the resistance of HSV-TK/GCV therapy. In the present study, it was explored whether GCV and its more lipophilic derivative (1) could inhibit effluxing of another chemotherapeutic, methotrexate (MTX), out of the human breast cancer cells. Firstly, it was found that the combination of GCV and MTX was more hemocompatible than the corresponding combination with compound 1. Secondly, both GCV and compound 1 enhanced the cellular accumulation of MTX in MCF-7 cells, the MTX exposure being 13–21 times greater compared to the MTX uptake alone. Subsequently, this also reduced the number of viable cells (41–56%) and increased the number of late apoptotic cells (46–55%). Moreover, both GCV and compound 1 were found to interact with breast cancer resistant protein (BCRP) more effectively than multidrug-resistant proteins (MRPs) in these cells. Since the expression of BCRP was higher in MCF-7 cells than in MDA-MB-231 cells, and the cellular uptake of GCV and compound 1 was smaller but increased in the presence of BCRP-selective inhibitor (Fumitremorgin C) in MCF-7 cells, we concluded that the improved apoptotic effects of higher MTX exposure were raised mainly from the inhibition of BCRP-mediated efflux of MTX. However, the effects of GCV and its derivatives on MTX metabolism and the quantitative expression of MTX metabolizing enzymes in various cancer cells need to be studied more thoroughly in the future.     

An FEL-based microwave system for fusion

This paper describes designs for 280-GHz and 560-GHz microwave sources based on free electron lasers (FELs). These 10-MW units are based on technology developed over the last 5 years. A first demonstration of high-average-power microwave production with an FEL system is expected in the Microwave Tokamak Experiment (MTX) facility. This paper gives details on the design and construction of that 250-GHz, 2-MW system and discusses specific applications for the Compact Ignition Tokamak (CIT).     

Combination of β-cyclodextrin inclusion complex and self-microemulsifying drug delivery system for photostability and enhanced oral bioavailability of methotrexate: novel technique

In the present study, we prepared an inclusion complex of methotrexate (MTX) with β-cyclodextrin (β-CD) in order to decrease its photosensitivity and enhance its aqueous solubility. Then we incorporated this inclusion complex in a self-microemulsifying drug delivery system (SMEDDS) overall to increase its oral bioavailability. The inclusion complex has been prepared by freeze drying method and characterized by differential scanning calorimetry (DSC), ultraviolet (UV), and infrared (IR) spectroscopy assays. The proper molecular ratio of MTX/β-CD was found to be of 1:7, and the water-solubility of MTX was increased in an average of 10-fold. The photostability studies showed that the MTX became stable on exposure to light. Construction of pseudoternary diagrams were investigated to prepare a MTX/β-CD inclusion complex loaded SMEDDS which was characterized by measuring the particle size and the zeta-potential. The optimum formulation of SMEDDS was a system consisting of ethyl oleate, tween 80, and propylene glycol with a mean droplet size of 39.42?nm. In vitro drug release in different pH media showed that the release profile of MTX from the MTX/β-CD loaded SMEDDS was influenced by the pH of the release medium and presented the characteristics of a sustained release profile. Finally, in-vivo studies showed an enhancement of the bioavailability of MTX from the MTX/β-CD loaded SMEDDS form of 1.57-fold. We concluded that the β-CD inclusion complex loaded SMEDDS improved the chemical and physiological properties of MTX and could be a promising means for the delivery of MTX and other unstable and lipophilic drugs by oral route.     

Co‐delivery of methotrexate and doxorubicin via nanocarriers of star‐like poly(DMAEMA‐block‐HEMA‐block‐AAc) terpolymers

Combined therapy is a promising strategy for clinical cancer treatment with synergistic effects. The purpose of the work reported was to evaluate a smart nanocarrier for co‐delivery of doxorubicin (DOX) and methotrexate (MTX). Since star‐like nanocarriers can load a high dose of drugs with various properties, we developed star polymer nanomicelles based on poly[(2,2‐dimethylaminoethyl methacrylate)‐block‐(2‐hydroxyethyl methacrylate)‐block‐(acrylic acid)] having potential for multi‐drug delivery. The nanomicelles demonstrated high encapsulation efficiency, i.e. 97.1% for DOX and 79.5% for MTX. To this end, the star‐like terpolymers were synthesized via atom transfer radical polymerization with pentaerythritol as an initiator. The micellar properties and dual stimuli‐responsive behaviour of the terpolymers were investigated using transmission electron microscopy, field emission scanning electron microscopy and dynamic light scattering measurements, concluding that this co‐therapy offers a promising approach for cancer treatment. © 2019 Society of Chemical Industry     

纳米技术在纺织品开发中的机遇和风险

论述了纳米技术产品的生命周期以及各方面的风险评估。对溶胶凝胶过程,包括其使用、应用以及由该技术生产的产品进行了详细的阐述。进一步证明了在当今已经可能以负责任的态度处理纳米材料。     

盐酸氨基葡萄糖及其与甲氨蝶呤联用对佐剂性关节炎大鼠的治疗作用

目的探讨盐酸氨基葡萄糖及其与甲氨蝶呤联用对佐剂性关节炎(AA)大鼠的治疗作用。方法将佐剂性关节炎大鼠分为4组:模型对照组(AA组)、盐酸氨基葡萄糖组(GH组)、甲氨蝶呤组(MTX组)和联合用药组(GHM组),另设1组空白对照。自造模前1d至造模后22d,正常对照组和AA组每天给予蒸馏水灌胃,其他组以相应的药物灌胃。造模前及造模后不同时间,测量各组大鼠左、右后足体积,造模后22d,ELISA法检测大鼠血清中肿瘤坏死因子-α(TNF-α)的含量。结果与AA组比较,在继发反应期,GH、MTX及GHM各组的左、右后足体积和血清中TNF-α含量均有所下降,且差异均有统计学意义,除血清中TNF-α含量GHM组显著低于MTX组外,其他各项指标GHM组与GH组和MTX组比较,差异均无统计学意义。结论盐酸氨基葡萄糖可缓解大鼠佐剂性关节炎症状,具有抗炎作用和治疗类风湿性关节炎的潜力,其与MTX联用,有望降低MTX的用量。     

煤机加工中数控系统界面的研究

煤炭机械加工中的数控机床的核心部件是数控系统,以构建的力士乐MTX数控系统为实验平台,利用系统提供的OPC数据接口,采用VB编程环境,遵循了模块化和开放性的思想,尝试建立一种能适于煤炭机械加工数控机床的客户界面。     

Methotrexate Alters the Expression of microRNA in Fibroblast-like Synovial Cells in Rheumatoid Arthritis

We aimed to investigate the effect of methotrexate (MTX) on microRNA modulation in rheumatoid arthritis fibroblast-like synovial cells (RA-FLS). RA-FLS were treated with MTX for 48 h. We then performed miRNA array analysis to investigate differentially expressed miRNAs. Transfection with miR-877-3p precursor and inhibitor were used to investigate the functional role of miR-877-3p in RA-FLS. Gene ontology analysis was used to investigate the cellular processes involving miR-877-3p. The production of cytokines/chemokines was screened by multiplex cytokine/chemokine bead assay and confirmed by ELISA and quantitative real-time PCR. The migratory and proliferative activities of RA-FLS were analyzed by wound healing assay and MKI-67 expression. MTX treatment altered the expression of 13 miRNAs (seven were upregulated and six were downregulated). Among them, quantitative real-time PCR confirmed that miR-877-3p was upregulated in response to MTX (1.79 ± 0.46-fold, p < 0.05). The possible target genes of miR-877-3p in RA-FLS revealed by the microarray analysis were correlated with biological processes. The overexpression of miR-877-3p decreased the production of GM-CSF and CCL3, and the overexpression of miR-877-3p inhibited migratory and proliferative activity. MTX altered the miR-877-3p expression on RA-FLS, and this alteration of miR-877-3p attenuated the abundant production of cytokines/chemokines and proliferative property of RA-FLS.