Opioid-based micro and nanoparticulate formulations: alternative approach on pain management

Context Opioids have been used as the reference treatment on chronic pain. However, they are related to serious adverse effects which affect the patient compliance to treatment, as well as, his quality of life. Particulate formulations have been investigated as an alternative to improve opioid efficacy and safety. Objective Summarise the available studies concerning micro and nanoencapsulated opioid formulations discussing their biopharmaceutical characteristics, such as composition, size, in vitro release, pharmacokinetic and antinociceptive profile. Methods Papers available in 1995–2015 at Medline, Science Direct and Web of Science databases were collected and assessed. Searches were performed using varied combinations of the keywords of this work. Results Opioid-loaded particles showed prolonged drug release with maintenance of serum therapeutic concentrations and extended analgesia when compared with the free drugs. The side effects incidences were reduced or maintained the same. Conclusion Particulate formulations can significantly increase both potency and safety profiles of opioids.     

钛质人工听小骨在开放式鼓室成形术中的疗效观察与应用体会

目的 探讨Ⅰ期钛质人工听小骨听力重建在慢性中耳炎和中耳胆脂瘤患者中的临床疗效及应用体会。 方法 回顾性分析行开放式鼓室成形术并接受Ⅰ期钛质人工听小骨听力重建的慢性中耳炎或中耳胆脂瘤患者65例临床资料,比较术前及术后1、3、6个月听力情况和气骨导差(ABG)。 结果 术后第1、3、6个月,纯音气导听阈均值(PTA)较术前降低,差异有统计学意义(P<0.05);术后6个月ABG均值较术前降低,差异具有统计学意义(P<0.05);术后ABG≤20 dB者达39耳(P<0.05)。 结论 开放式鼓室成形术加Ⅰ期钛质人工听小骨行听骨链重建治疗慢性中耳炎和中耳胆脂瘤能够有效提高患者的听力水平;选择适当的手术适应证、良好的手术技巧及围手术期处理是取得成功的保证。     

Elaboration and Characterization of WMoTaNb High Entropy Alloy Prepared by Powder Metallurgy Processes

This work concerns the sintering of tungsten-based (i.e WMoTaNb) high entropy alloy (HEA) powders using the spark plasma sintering (SPS) technique and their mechanical properties. The synthesis was performed by a self-propagating high-temperature synthesis (SHS) type reaction in which the mixture of metallic oxides (WO₃, MoO₃ …) is reduced by magnesium. For this, a specific reactor has been developed. Different conditions including the addition of a moderator were tested. These powders are then densified by SPS technology which allows for keeping the initial microstructure of the powder. The optimization of sintering conditions was performed with the objective to control simultaneously the chemical composition, the grain growth and the densification stages.     

载5-氟尿嘧啶聚乳酸纳米微粒对人眼球筋膜囊成纤维细胞抑制作用的研究

目的 探讨载5-氟尿嘧啶(5-FU)聚乳酸纳米微粒(5-FU-PLA-NPs)对体外培养的人眼球筋膜囊成纤维细胞的抑制作用.方法 为实验研究.噻唑蓝(MTT)比色法检测不同剂量(0.1、1.0、10.0、100.0和1000.0 mg/L)的空载聚乳酸纳米微粒(PLA-NPs)在不同时间点(48和72 h)对人眼球筋膜囊成纤维细胞增殖的影响,MTT比色法检测不同剂最(0.1、1.0、10.0、100.0和1000.0 mg/L)5-FU纳米药物和5-FU原药在1～7 d内共7个时间点对成纤维细胞生长的抑制作用,计算并比较两者在7个时间点对成纤维细胞的抑制率.RT-PCR分别检测剂量为100.0 mg/L的5-FU纳米药物和5-FU原药作用成纤维细胞1、5、7 d后Ⅲ型前胶原蛋白mRNA的表达情况.对同一天各浓度A值的比较用单因素方差分析,同一天相同浓度5-FU原药组A值与5-Fu-PLA-NPs组A值的比较用两独立样本t检验分析,采用单因素方差分析分别比较不同时间点各组COI3的相对A值.结果 空载聚乳酸纳米微粒对成纤维细胞的增殖没有影响.载5-FU纳米微粒和5-FU原药均抑制成纤维细胞的增殖,并使Ⅲ型前胶原蛋白mRNA的表达水平降低,该抑制作用具有时间和剂量依赖性.作用初期各剂量组5-FU纳米微粒的抑制作用低于原药,随时间延长抑制作用超过原药,差异有统计学意义(P<0.05).结论 聚乳酸(PEA)具有良好的生物相容性与安全性,可作为眼部用药的载体.载5-FU聚乳酸纳米微粒具有一定的缓释功能,可长期释放药物,随着作用时间的延长,5-FU纳米药物对成纤维细胞的抑制作用超过原药,其可作为靶向缓释药物载体.(中华眼科杂志,2009,45:26-31)     

姜黄素抑制磨损颗粒诱导炎性介质产生及作用机制

目的观察姜黄素对磨损颗粒刺激炎性介质产生的影响,进一步探讨炎性介质表达调节机制。方法构建小鼠air-pouch动物模型成功后,于囊腔中注射高分子聚乙烯颗粒悬液。随机分为实验组和对照组,分别每日每次0.6ml,浓度为3.2g.L-1姜黄素溶液灌胃和等量6%的聚乙二醇溶液灌胃,共2wk,给药后2wk处死取材,进行组织学观察,采用ELISA法及半定量RT-PCR检测假体周围组织中TNF-浕、IL-1β、EMMPRIN、MMP-9的表达。Western blot检测囊壁组织核蛋白中NF-κBP65蛋白的表达。结果组织学观察发现对照组的囊腔范围及囊壁厚度明显大于给药组。HE染色囊壁中有大量炎性细胞,两组间炎性细胞计数差异有统计学意义;两组囊壁组织中TNF-浕、IL-1β、EMMPRIN、MMP-9、NF-κBP65表达有统计学意义。结论姜黄素可以抑制air-pouch动物模型界膜组织中TNF-浕、IL-1β、EMMPRIN、MMP-9的表达,可能是通过下调囊壁组织中核蛋白NF-κB完成的。     

6种中药注射剂在输液中的不溶性微粒测定

目的:测定6种中药注射剂加入输液后的不溶性微粒。方法:采用2005年版《中国药典》规定的不溶性微粒检查法——光阻法测定6种中药注射剂在输液中的不溶性微粒。结果:6种中药注射剂均含有不同粒径和不同数量的不溶性微粒。结论:应加强中药静脉注射剂的质量控制,在使用中密切注意不溶性微粒的监控。     

Inflammatory effects of coarse and fine particulate matter in relation to chemical and biological constituents

There is conflicting evidence in the literature as to the predominant mechanism and also the compositional element(s) that drives the pulmonary inflammatory response of ambient particulate matter (PM). We have investigated the inflammogenic potential of coarse (2.5-10 microm) and fine (<2.5 microm) PM from both a rural and an industrial location in Germany, using bronchoalveolar lavage (BAL) of rat lungs 18 h post intratracheal instillation with PM. Irrespective of the sampling location, the coarse fraction of PM(10) but not its fine counterpart caused neutrophilic inflammation in rat lungs, in the absence of any severe pulmonary toxicity as indicated by the lack of an increase in lavage protein and lactate dehydrogenase levels. The rural sample of coarse PM also caused a significant increase in the tumor necrosis factor alpha (TNFalpha) content as well as glutathione depletion in the BAL fluid. The contrasting inflammatory responses of the different samples could not be explained by differences in the concentrations of soluble Fe, Cu, V, Ni, Cr, or Al or by the.OH generating capacities of the PM suspensions. However, the effects of the different PM samples were clearly associated with their endotoxin content, as well as their ability to induce interleukin (IL)-8 and TNFalpha from whole blood in vitro. In conclusion, on an equal mass basis, coarse but not fine PM samples from our sampling campaign induced an inflammatory reaction in the lung in the absence of gross cellular lung damage, following intratracheal instillation. Our data also indicate, in accordance with previous independent in vitro observations, that endotoxin or related contaminants may play a role in these in vivo effects.     

基于CAD/CAM技术的钛合金制品在正颌外科手术中应用研究进展

计算机辅助设计与计算机辅助制作(computer aided design and computer aided manufacturing,CAD/CAM)技术发展迅速,在医学领域尤其是外科领域已被广泛应用.正颌外科是外科学的重要组成部分,其对于治疗的精度与材料的质量要求严格,而基于CAD/CAM技术的钛合金制品(如...     

Cancer targeted drug delivery using active low-density lipoprotein nanoparticles encapsulated pyrimidines heterocyclic anticancer agents as microtubule inhibitors

Recently, nanomedicine had the potential to increase the delivery of active compounds to specific cell sites. Nano-LDL particles are recognized as an excellent active nano-platform for cancer-targeted delivery. Loading of therapeutic agents into nano-LDL particles achieved by surface loading, core loading, and apolipoprotein-B100 interaction. Therefore, loading nano-LDL particles’ core with pyrimidine heterocyclic anticancer agents will increase cancer cytotoxic activity targeting tubulin protein. First, by mimicking the native LDL particle''s metabolic pathway, and second the agent’s chemical functional groups like the native amino acids cytosine and thymine structures will not be recognized as a foreign entity from the cell’s immune system. Nano-LDL particles will internalize through LDL-receptors endocytosis and transport the anticancer agent into the middle of the cancer cell, reducing its side effects on other healthy cells. Generally, the data revealed that pyrimidine heterocyclic anticancer agents’ size is at the nano level. Agents’ morphological examination showed nanofibers, thin sheets, clusters, and rod-like structures. LDL particles’ size became bigger after loading with pyrimidine heterocyclic anticancer agents and ranged between 121.6 and 1045 nm. Then, particles were tested for their cytotoxicity against breast (MDA468) and prostate (DU145) cancer cell lines as surrogate models with dose-response study 10, 5, 1 µM. The IC₅₀ values of the agents against DU145 and MDA468 possessed cell growth inhibition even at the 1 µM concentration ranges of 3.88 ± 1.05 µM and 3.39 ± 0.97 µM, respectively. In sum, nano-LDL particles proved their efficiency as active drug delivery vehicles to target tubulin in cancer cells.     

Refinement of the Magnesium–Aluminium Alloy Microstructure with Zirconium

The magnesium–aluminium alloy AZ91 was inoculated with zirconium to refine the microstructure. Six different concentrations of zirconium content were tested, ranging from 0.1 to 0.6 wt %, and compared to the baseline AZ91 alloy without modification. Melted metal was poured into a preheated ceramic mould and the temperature was measured and recorded during the solidification. The derivative and thermal analysis (DTA) was performed to compare the crystallisation dynamics. Formed microstructure was analysed using an optical microscope, scanning electron microscopy (SEM-EDX) and energy dispersive X-ray spectrometry (XRD). The chemical composition was measured using an arc spectrometer. The time of solidification was shortened for the samples with a concentration of zirconium 0.3 wt % and the microstructure was refined. The level of grain refinement remained below 10% and the grain shape was changed to more spherical shapes. Both the primary magnesium and eutectic phases were modified. However, at a low concentration of zirconium (0.1 and 0.2 wt %), the primary grain size was increased. Therefore, the optimal zirconium concentration was 0.3 wt %. Larger concentrations (0.4 to 0.6 wt %) did not provide any additional benefit. Theoretical analysis showed that some Al₃Zr intermetallic phases can form, which was confirmed on the derivate curve of the thermal analysis, and SEM-EDS and XRD analyses.