Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas

Although there are many patients with brain tumors worldwide, there are numerous difficulties in overcoming brain tumors. Among brain tumors, glioblastoma, with a 5-year survival rate of 5.1%, is the most malignant. In addition to surgical operations, chemotherapy and radiotherapy are generally performed, but the patients have very limited options. Temozolomide is the most commonly prescribed drug for patients with glioblastoma. However, it is difficult to completely remove the tumor with this drug alone. Therefore, it is necessary to discuss the potential of anticancer drugs, other than temozolomide, against glioblastomas. Since the discovery of cisplatin, platinum-based drugs have become one of the leading chemotherapeutic drugs. Although many studies have reported the efficacy of platinum-based anticancer drugs against various carcinomas, studies on their effectiveness against brain tumors are insufficient. In this review, we elucidated the anticancer effects and advantages of platinum-based drugs used in brain tumors. In addition, the cases and limitations of the clinical application of platinum-based drugs are summarized. As a solution to overcome these obstacles, we emphasized the potential of a novel approach to increase the effectiveness of platinum-based drugs.     

色谱技术在中药标准品制备中的应用

色谱技术是天然产物研究中重要的分离和纯化方法。本文介绍了色谱法，并综述了其在中药标准品制备中的应用，最后对此进行了展望。     

天然药物在现代医疗保健中的地位和作用

世界天然药物市场主要集中在美国、欧洲和亚洲三大区域,全球植物药市场的年销售额已达270亿美元。在过去的10年间,以植物制剂为主体的天然药物开始走俏西方。面对“回归自然”的世界潮流,采用现代科学技术,实现中药现代化和国际化,将为人类现代医疗保健做出重大贡献。     

Fe3O4-10-HCPT及Fe3O4-HCPT@SiO2核壳纳米粒子的制备

为有效控制磁性四氧化三铁纳米粒子在水介质中的分散,防止其聚集.通过控制Na Cl溶液的物质的量浓度,对比研究磁性四氧化三铁纳米粒子在超声前和超声后在盐中的分散情况.实验结果表明,磁性四氧化三铁纳米粒子在0.4 mol/L的氯化钠中分散性最好,聚集度较小;进一步为了制备粒径均匀的复合磁性纳米载药粒子,通过调节10-羟基喜树碱溶液的p H,将10-羟基喜树碱和磁性纳米粒子制备成复合纳米粒子,并将其用二氧化硅包覆制备了复合载药纳米粒子,其复合纳米粒子的粒径大约为120 nm,结果显示通过该方法成功制备了理想的磁性纳米载药粒子.     

Characterisation of flucloxacillin and 5-hydroxymethyl flucloxacillin haptenated HSA in vitro and in vivo

Flucloxacillin is a synthetic penicillin used in the treatment of Staphylococcal infections. Adverse reactions to the drug are believed to arise through covalent modification of proteins, with tissue damage occurring secondary to an immune reaction. Serum proteins have been shown by adduct-specific antibodies to be modified by flucloxacillin, but the nature and sites of modification have not been characterised. Here, in vitro studies on HSA have shown by MS that the modification of protein lysine residues occurs in a dose-, time- and site-dependent manner. Affinity, cation exchange and reversed phase chromatography prior to MS revealed in vivo modification of HSA with flucloxacillin in tolerant patients, with up to nine modified lysine residues being detected in each patient, and with modification of Lys190 and Lys212 being detected in 8/8 patients. It was also revealed for the first time that plasma proteins could be modified with the 5-hydroxymethyl metabolite of flucloxacillin, and that essentially the same Lys residues were targeted by both the parent drug and its metabolite. This study provides a detailed characterisation of sites of chemical modification of an endogenous target and reveals candidate peptides for T-cell and antibody assays of flucloxacillin hypersensitivity.     

The application of inductively coupled plasma mass spectrometry in clinical pharmacological oncology research

Metal-based anticancer agents are frequently used in the treatment of a wide variety of cancer types. The monitoring of these anticancer agents in biological samples is important to understand their pharmacokinetics, pharmacodynamics, and metabolism. In addition, determination of metals originating from anticancer agents is relevant to assess occupational exposure of health care personnel working with these drugs. The high sensitivity of inductively coupled plasma mass spectrometry (ICP-MS) has resulted in an increased popularity of this technique for the analysis of metal-based anticancer drugs. In addition to the quantitative analysis of the metal of interest in a sample, ICP-MS can be used as an ultrasensitive metal selective detector in combination with speciation techniques such as liquid chromatography. In the current review we provide a systematic survey of publications describing the analysis of platinum- and ruthenium-containing anticancer agents using ICP-MS, focused on the determination of total metal concentrations and on the speciation of metal compounds in biological fluids, DNA- and protein-adducts, and environmental samples. We conclude that ICP-MS is a powerful tool for the quantitative analysis of metal-based anticancer agents from multiple sample sources.     

Drug self-assembly: A phenomenon at the nanometer scale with major impact in the structure–biological properties relationship and the treatment of disease

Under water-rich conditions, small amphiphilic and hydrophobic drug molecules self-assemble into supramolecular nanostructures. Thus, substantial modifications in their interaction with cellular structures and the ability to reach intracellular targets could happen. Additionally, drug aggregates could be more toxic than the non-aggregated counterparts, or vice versa. Moreover, since self-aggregation reduces the number of effective “monomeric” molecules that interact with the target, the drug potency could be underestimated. In other cases, the activity could be ascribed to the non-aggregated molecule while it stems from its aggregates. Thus, drug self-assembly could mislead from drug throughput screening assays to advanced preclinical and clinical trials. Finally, aggregates could serve as crystallization nuclei. The impact that this phenomenon has on the biological performance of active compounds, the inconsistent and often controversial nature of the published data and the need for recommendations/guidelines as preamble of more harmonized research protocols to characterize drug self-aggregation were main motivations for this review. First, the key molecular and environmental parameters governing drug self-aggregation, the main drug families for which this phenomenon and the methods used for its characterization are described. Then, promising nanotechnology platforms investigated to prevent/control it towards a more efficient drug development process are briefly discussed.     

Evaluating spray gelation and spray freeze drying as the granulation method to prepare oral tablets of amorphous drug nanoplex

Amorphous drug nanoplex represents one of the most promising solubility enhancement strategies of poorly-soluble drugs. Solubility enhancement capability of nanoplex hitherto has been demonstrated for nanoplex suspension and lyophilized/spray-dried nanoplex, but not for its oral tablets. Using ciprofloxacin as the model poorly-soluble drug, we investigated spray gelation (SG) of alginate and spray freeze drying (SFD) with cryoprotective mannitol, as the nanoplex’s granulation methods. Both granules were evaluated in terms of their morphology, physical form, flowability, drug content, preparation yield, dissolution profile, drug solubility enhancement, and storage stability. Subsequently, tablets of the granules were prepared and characterized in terms of their drug content uniformity, weight variation, friability, hardness, dissolution profile, and solubility enhancement. The results showed that nanoplex in SG granules was embedded in dense amorphous alginate matrix, while nanoplex in SFD granules was dispersed in porous crystalline mannitol particles. Despite their distinct morphology, physical form, and dissolution profile, the two granules exhibited similar drug solubility enhancements. Both granules were readily compacted into tablets with minimal changes in their dissolution and solubility enhancement after tableting. The present work demonstrated SG and SFD as viable granulation methods of nanoplex, with SG granules exhibiting superior flowability, stability, but lower yield.     

Development and applications of surface-activated chemical ionization

This review regards the recently developed ionization source named surface-activated chemical ionization (SACI) that employs an interaction with a surface placed at low voltage for the activation of the ionization of sample molecules to increase the sensitivity in the analysis of various compounds of biological and clinical interest. These results are due to the strong chemical noise decrease and the increase of ionization efficiency. This ionization source has been employed for the analysis of various compounds of different molecular mass and polarity (addicted and pharmaceutical drugs, amino acids, steroids, peptides, and proteins). The SACI development theoretical mechanism, benefits, disadvantages, applications, and future developments are reported and discussed.     

液相色谱-二极管阵列检测法同时测定血液中6种毒品及其代谢物

建立了一种同时测定血液中吗啡、苯丙胺类、氯胺酮和杜冷丁等6种常见毒品的液相色谱-二极管阵列检测器联用的定性定量方法。条件为以乙腈和0.005mol/L的磷酸二氢钾水溶液为流动相,梯度洗脱,经C18色谱柱分离,二极管阵列检测器检测,检测波长210nm。利用保留时间和紫外吸收光谱进行定性分析。血浆中6种毒品在8.0～200.0ng/mL范围内线性关系良好（r2=0.999 2）,回收率范围为68.9%～95.2%,检测限为3.3ng/mL。结果表明,该方法操作简便、快速、选择性强、灵敏度高,适于血液中6种常见毒品及其代谢物的分析,可为相关案件提供方法和技术支持。