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.     

Formulation and development of ophthalmic in situ gel for the treatment ocular inflammation and infection using application of quality by design concept

Context: The conventional liquid ophthalmic delivery systems exhibit short pre-corneal residence time and the relative impermeability to the cornea which leads to poor ocular bioavailability.

Objective: The aim of this study was to apply quality by design (QbD) for development of dexamethasone sodium phosphate (DSP) and tobramycin sulfate (TS)-loaded thermoresponsive ophthalmic in situ gel containing Poloxamer 407 and hydroxyl propyl methyl cellulose (HPMC) K4M for prolonging the pre-corneal residence time, ocular bioavability and decreases the frequency of administration of dosage form. The material attributes and the critical quality attributes (CQA) of the in situ gel were identified. Central composite design (CCD) was adopted to optimize the formulation.

Materials and methods: The ophthalmic in situ forming gels were prepared by cold method. Materials attributes were the amount of Poloxamer 407 and HPMC and CQA identified were Gel strength, mucoadhesive index, gelation temperature and % of drug release of both drug.

Results and discussion: Optimized batch (F*) containing 16.75% poloxamer 407 and 0.54% HPMC K4M were exhibited all results in acceptable limits. Compared with the marketed formulation, optimized in situ gel showed delayed T_max, improved C_max and AUC in rabbit aqueous humor, suggesting the sustained drug release and better corneal penetration and absorption.

Conclusion: According to the study, it could be concluded that DSP and TS would be successfully formulated as in situ gelling mucoadhesive system for the treatment of steroid responsive eye infections with the properties of sustained drug release, prolonged ocular retention and improved corneal penetration.     

TMCP工艺对X100管线钢M/A岛的影响

M/A岛是X100管线钢典型组织,对钢的强韧性有着重要的影响。利用热模拟和显微分析技术研究了冷却速度、变形量和等温温度对X100管线钢中M/A岛的影响规律。结果表明:随着冷速增加,M/A岛体积分数和平均尺寸都减小,由在晶界处分布的较大块状向板条间隙弥散分布的细小片层状转变;随着变形量增加,M/A岛体积分数先增加,变形量为40%达到最大,变形量达到50%时,M/A岛体积分数降低;快冷后随着等温温度升高,M/A岛平均尺寸增大,等温温度为450℃时体积分数最大,温度继续升高体积分数减小。观察到M/A岛形貌多呈棱角状、链条状、片条状和针状,分布在晶界和基体内,岛内精细结构观察到微孪晶马氏体。     

超超临界锅炉材料TP310HCbN(HR3C)持久及析出行为

采用持久试样方法,结合Gleeble、硬度分析、SEM、EDS、TEM等分析手段,对TP310HCbN耐热钢热变形以及在650℃与700℃条件下持久及析出行为进行了分析。结果表明:两种持久温度条件下,硬度变化趋势差别不大;随着持久时间延长,TP310HCbN耐热钢晶内析出物由颗粒状转变为棒状,并存在大量与位错相互作用的蠕虫状NbCrN析出物;太钢生产的TP310HCbN耐热钢650℃/700℃-100000h外推持久强度均满足标准要求。     

深冷处理对AISI 310S不锈钢耐腐蚀磨损性能的影响

研究了深冷处理对AISI 310S不锈钢在3.5%(质量分数)Na Cl溶液中耐腐蚀磨损性能的影响,将310S不锈钢在-196℃进行保温深冷处理,结果表明:相对未深冷处理,深冷处理之后,材料的晶粒得到细化,更多碳化物弥散析出基体;深冷处理之后材料的耐腐蚀性能得到提高,在深冷处理4 h时达到最佳值,相比未深冷处理,自腐蚀电位从-0.525 V提高到-0.423 V,提升了19.4%;且深冷处理之后,材料的耐腐蚀磨损性能得到提升,经过深冷处理4 h,材料的磨损率从120×10-6mm3/Nm降低到63×10-6mm3/Nm,降低90%。     

物联网与感知矿山专题讲座之四——感知矿山物联网与煤炭行业物联网规划建设

指出感知矿山物联网M2M平台应为应用层服务提供开放的接口,适应完善安全避险"六大系统"、领导带班下井、煤矿灾害监测的需求;给出了煤炭行业物联网的四层结构,指出感知矿山物联网建设是整个煤炭行业物联网建设的重点,其它层次以煤矿安全管理和资源管理为主,并分析了矿业集团级、省级、国家级煤炭行业物联网的应用方式;提出了煤炭行业物联网建设需要注意的问题。     

基于WCDMA的矿用M2M终端系统的设计

为了将井下人员信息、设备信息以及环境信息通过井下现有的通信网络传送至煤矿信息中心,提出了一种基于WCDMA的矿用M2M终端系统的设计方案,详细介绍了该系统硬件和软件的设计。该系统实现了对井下目标信息的采集、人机交互操作及数据通信功能,通过WCDMA网络将采集的数据互传,实现了物与物相联、物与人相联以及物与网络相联的物联网。     

无线传感器网络汇聚节点LAN接口设计与实现

分析了无线传感器网络汇聚节点的通信功能需求,设计了基于PXA310核心处理器及10M/100M自适应DM9000以太网控制芯片的LAN接口硬件方案,满足了无线传感器网络汇聚节点数据可靠性传输的以太网通信结构;然后研究了在Linux平台下网络驱动程序的体系架构以及数据包的发送接收过程,并实现了基于设计的硬件平台汇聚节点以太网的驱动程序开发和具体的移植过程,实现嵌入式系统和设计的以太网硬件平台通讯功能;经实际应用表明设计汇聚节点的LAN接口能快速稳定传输数据。     

实时光纤网络中突发数据传输的物理层设计

使用Altera CycloneⅢ FPGA设计了百兆实时光纤网络物理层,解决了百兆光纤网络突发数据通信中的数据突发发送、数据时钟的恢复及接收的关键技术。利用空间过采样技术避开了光通信中用于相位锁定、时钟恢复所需的等待时间,直接从码流中提取数据,从而减少了网络突发数据包的同步码开销,提高了光网络的带宽利用率。