Dynamic Microcapsules with Rapid and Reversible Permeability Switching

Dynamic microcapsules are reported that exhibit shell membranes with fast and reversible changes in permeability in response to external stimuli. A hydrophobic anhydride monomer is employed in the thiol–ene polymerization as a disguised precursor for the acid‐containing shells; this enables the direct encapsulation of aqueous cargo in the liquid core using microfluidic fabrication of water‐in‐oil‐in‐water double emulsion drops. The poly(anhydride) shells hydrolyze in their aqueous environment without further chemical treatment, yielding cross‐linked poly(acid) microcapsules that exhibit trigger‐responsive and reversible property changes. The microcapsule shell can actively be switched numerous times between impermeable and permeable due to the exceptional mechanical properties of the thiol–ene network that prevent rupture or failure of the membrane, allowing it to withstand the mechanical stresses imposed on the capsule during the dynamic property changes. The permeability and molecular weight cutoff of the microcapsules can dynamically be controlled with triggers such as pH and ionic environment. The reversibly triggered changes in permeability of the shell exhibit a response time of seconds, enabling actively adjustable release profiles, as well as on‐demand capture, trapping, and release of cargo molecules with molecular selectivity and fast on‐off rates.     

Microfluidic Fabrication of Capsule Sensor Platform with Double‐Shell Structure

Metal nanoparticles are frequently employed for the colorimetric detection of specific target molecules using an aggregation‐induced shift of the localized surface plasmon resonance. However, metal nanoparticles dispersed in bulk solutions are prone to be contaminated by adhesive molecules and the dispersions tend to be diluted by sample fluids, restricting direct application to unpurified pristine samples. Here, a versatile capsule sensor platform is proposed that can encompass a variety of different types of nanoparticle‐based sensors. The capsule sensors are microfluidically prepared to obtain close control over their dimensions and composition. Their aqueous cores that are loaded with sensing materials are surrounded by an ultrathin inner oil shell and an outer hydrogel shell. The hydrogel shell prevents the diffusion of large adhesive molecules into the core, thereby preventing contamination of the sensing materials. The oil shell is selectively permeable such that it further improves the sensor selectivity. Importantly, these shells confine the sensing materials and prevent them from being diluted, securing a consistent optical property. Moreover, the capsule‐based sensors display a higher sensitivity than bulk dispersions because a smaller amount of sensing materials is used. The power of nanoparticle‐loaded capsule sensors is demonstrated using lysine‐coated gold nanoparticles to detect mercury ions.     

Template‐Mediated Assembly of DNA into Microcapsules for Immunological Modulation

There is a need for effective vaccine delivery systems and vaccine adjuvants without extraneous excipients that can compromise or minimize their efficacy. Vaccine adjuvants cytosine–phosphate–guanosine oligodeoxynucleotides (CpG ODNs) can effectively activate immune responses to secrete cytokines. However, CpG ODNs are not stable in serum due to enzymatic cleavage and are difficult to transport through cell membranes. Herein, DNA microcapsules made of CpG ODNs arranged into 3D nanostructures are developed to improve the serum stability and immunostimulatory effect of CpG. The DNA microcapsules allow encapsulation and co‐delivery of cargoes, including glycogen. The DNA capsules, with >4 million copies of CpG motifs per capsule, are internalized in cells and accumulate in endosomes, where the Toll‐like receptor 9 is engaged by CpG. The capsules induce up to 10‐fold and 20‐fold increases in tumor necrosis factor (TNF)‐α and interleukin (IL)‐6 secretion, respectively, in RAW264.7 cells compared with CpG ODNs. Furthermore, the microcapsules stimulate TNF‐α and IL‐6 secretion in a concentration‐ and time‐dependent manner. The immunostimulatory activity of the capsules correlates to their intracellular trafficking, endosomal confinement, and degradation, assessed by confocal and super‐resolution microscopy. These DNA capsules can serve as both adjuvants to stimulate an immune reaction and vehicles to encapsulate vaccine peptides/genes to achieve synergistic immune effects.     

基于YOLOv4算法的药用空心胶囊表面缺陷检测方法

目的 为提升质检过程中药用空心胶囊的表面缺陷检测精度及其自动化水平。方法 通过设计高质量图像采集方案来避免胶囊表面出现光斑,以此构建药用空心胶囊缺陷数据集。基于YOLOv4算法,建立深度学习检测模型,利用多尺度特征提取以及训练策略,增强对小目标缺陷检测的鲁棒性。采用K-means++聚类算法更新锚框初始值,以提高模型对胶囊表面缺陷的预测性能。结果 实验结果表明,提出的胶囊缺陷检测方法能够准确判别胶囊好坏,并能检测出其表面的凹陷、孔洞、划痕、污点和接口缺损等5类缺陷,其中对于胶囊有无缺陷的平均精确均值达99.05%,各缺陷类型的平均精确率为91.81%,而每秒检测图像可达22张。与其他典型的目标检测方法相比,文中方法在检测速度和精度上都有一定优势。结论 文中所提出的基于YOLOv4的缺陷检测方法实现了对药用空心胶囊多类型缺陷的分类与定位,具有较好的检测效果和稳定性,在满足生产质量管控要求的同时,可大幅降低人工成本。     

会议厅兼作音乐厅——广州白云国际会议中心岭南大会堂建筑声学设计

广州白云国际会议中心是广东省召开省、市人大、政协等政务会议的重要场所,是广东省、广州市的重要公共建筑设施,总投资约40亿元人民币,于2005年10月26日正式动工建设,2007年2月建成投入使用。其中的1200座岭南大会堂除了考虑举行会议的功能外,还用于室内乐和交响乐演出。该会堂配有电声系统,实现了在较长混响时间的条件下,通过合理选择、布置扬声器系统,但不采用可调混响设施,达到兼顾音乐的丰满度和语言的清晰度要求,既能满足举办音乐会演出的需要,又满足举办会议需要的设计目标。该会堂建成投入使用后,已成功举办了多场音乐会和会议,成为广州地区又一重要音乐演出场所。     

Hard gelatin and hypromellose (HPMC) capsules: estimation of rupture time by real-time dissolution spectroscopy

The objective of this study was to measure rupture time of gelatin and hypromellose (hydroxypropyl methylcellulose or HPMC) capsules using a novel approach based on real-time dissolution spectroscopy. Rupture time was measured in standard dissolution apparatus at a constant temperature using a dip-type fiber-optic probe. Labrasol released from the capsules was treated as the marker of the rupture process. Light scatter generated by the emulsified labrasol was detected by an ultrafast monochromator at scan rates approximating 24,000 nm/min. This technique was validated by measuring the dissolution time of gelatin capsules. Rupture times of hypromellose capsules were studied as a function of capsule size, capsule grade, and dissolution medium. Statistical correlations were analyzed by ANOVA. Rupture time of hypromellose capsules was dependent on both the medium and the grade of the capsule, and was independent of capsule size. The composition of the dissolution medium contributes to the rupture time of the capsules and should be considered when fast release and quick biological response is desired. Release delay, however, may not manifest itself in vivo and the time to maximum plasma concentration may not be significant.     

分光光度法测定洋参软胶囊中人参总皂甙

目的建立分光光度法测定洋参软胶囊中人参总皂甙的含量的分析方法。方法通过超声辅助加热的方式对洋参软胶囊中人参总皂甙进行提取,在-0.08 Mpa 60℃条件下快速旋转蒸发洗脱液,采用多点校正分光光度法进行测定。结果总皂甙在0~50μg/m L浓度范围内线性良好,相关系数r2为0.9991。3个水平下的加标回收率为90.0%~98.9%,相对标准偏差小于2.3%,精密度、回收率均满足实验要求。结论该法简单快速、准确可靠,可作为洋参软胶囊中总皂甙的质量评价方法。     

Evaluation and comparison of physicomechanical characteristics of gelatin and hypromellose capsules

The aim of this study is evaluation and comparison of physical and mechanical properties of hypromellose and gelatin capsules. For this purpose, the empty and filled capsules of hypromellose and gelatin (size 4) were examined in regard with their physical and mechanical characteristics, employing textural analysis, and disintegration properties in various immersion fluids, utilizing a USP 28 disintegration apparatus. The results demonstrated that owing to their greater water permeability, gelatin capsules disintegrate much faster than hypromellose shells in all tested media. However, hypromellose capsules showed a more uniform pattern of dispersion in the disintegration fluids. As for mechanical properties, at ambient conditions, gelatin capsules appeared to be harder and stronger with less elasticity as compared with hypromellose shells. On the contrary, at an elevated temperature, gelatin capsules demonstrated lower resilience. This study shows that hypromellose capsules have excellent properties and are promising as far as regulatory, manufacturing, religious, and dietary issues are concerned.     

pH-sensitive capsules as intracellular optical reporters for monitoring lysosomal pH changes upon stimulation

The concept of a long-term sensor for ion changes in the lysosome is presented. The sensor is made by layer-by-layer assembly of oppositely charged polyelectrolytes around ion-sensitive fluorophores, in this case for protons. The sensor is spontaneously incorporated by cells and resides over days in the lysosome. Intracellular changes of the concentration of protons upon cellular stimulation with pH-active agents are monitored by read-out of the sensor fluorescence at real time. With help of this sensor concept it is demonstrated that the different agents used (Monensin, Chloroquine, Bafilomycin A1, Amiloride) possessed different kinetics and mechanisms of action in affecting the intracellular pH values.