用于微流体驱动用的微型文氏管的结构优化

为了给组织液的透皮抽取提供负压值,本文研究了结构简单、加工方便的PDMS微型文氏管的优化设计．首先理论推导了文氏管的结构参数对输出负压的影响规律,然后采用Fluent进行模拟计算,接着用模塑法设计加工了PDMS文氏管,并搭建了文氏管输出负压的检测系统,最后对实验结果进行分析讨论．通过对比测量,给出了适用于本文的微型化文氏管结构,即喉管长×宽×高为6mm×0．25mm×0．25mm、收缩角30°、扩散角30°．本文设计加工的文氏管在220kPa的正压下可输出87kPa的负压,提高了组织液透皮抽取的效率．该微型文氏管同以往的真空发生装置相比既能满足系统小型化和集成化要求,又能在相对较小的输入压强下,为组织液透皮抽取提供足够高的真空负压输出,为驱动微管路内流体输运提供足够大的抽取速率．     

低频超声的应用基础研究进展

低频超声具有治疗价值,近年来随着低频超声研究的深入,其作用机制尤其空化效应逐渐被广泛接受。文章围绕透皮给药,促进慢性伤口愈合及抗肿瘤治疗三个方面,介绍低频超声的研究进展。今后如何将低频超声更好地运用至临床工作中,且在保证安全性的基础上进一步提高原有治疗效果将是研究者未来共同努力的方向。     

真空技术在真空排污系统中的应用

真空排污系统是利用负压管道中的负压梯度将用户处排放的污水逐步输送、收集至真空站后集中处理及排放的污水收集系统。综述了真空排污系统的分类及适用范围,真空的获得及真空检漏测试的标准。介绍了真空排污系统中用户终端的形式和关键阀件。简述了真空排水管网的输送机理。比较了不同的真空罐排放方式及其技术关键。     

长春新碱透皮给药系统筛选及其透皮机理研究

分别制备了含不同表面活性剂的载长春新碱传递体(VCR-T)和载长春新碱壳聚糖纳米粒(VCR-CS-NPs),通过体外透皮试验,比较了不同透皮给药系统的透皮效果,并用DSC扫描探索了透皮效果差异的原因.所制备的VCR-T包封率从50%至80%不等,粒径90nm左右;VCR-CS-NPs的包封率为50%,粒径200nm左右;透射电镜下观察VCR-T和VCR-CS-NPs均外形圆整光滑,不粘连.体外透皮结果显示含Brij78的VCR-T为最佳的VCR透皮给药系统,DSC扫描认为这与载体与Brij78的相互作用有关;VCR-CS-NPs不能很好地透过皮肤,这可能与其粒径较大有关.     

上海光源(SSRF)输运线真空系统设计

本文介绍了上海光源高能输运线和低能输运线真空系统设计,包括总体布局,真空盒的结构和真空获得系统.低能输运线由两个弯段和三个直线段组成,高能输运线由五个弯段和四个直线段组成.用有限元方法分析计算了输运线弯段真空盒的大气负载变形,以确定真空盒的形状和尺寸,结果变形量小于0.15 mm.通过模拟输运线全段真空盒的压强分布来优化泵系统的布局,结果表明全线压强小于6×10-6 Pa.因此真空系统的设计方案能满足物理指标和实际工程要求.     

用于药物传输的MEMS平面金属微针

介绍了传统给药方式的局限性、微针应用于新的药物传输方式——透皮给药的优点以及微针的特点,并提出了一种基于微机电系统技术制作同平面金属微针的方法.采用该方法可制备实心微针和空心微针.这两种金属微针均采用电镀技术制作,既降低了成本又提高了微针的强度.微针为楔形,边缘比较光滑,针尖有较锋利的尖端,改善了刺入皮肤的效果;针体长度400μm,厚度50μm,其中空心微针中的微流道宽度为50μm.此类微针便于改变尺寸以满足不同的需要.用该微针进行了刺入鼠皮的实验,验证了该微针刺入皮肤的有效性.     

微创伤血糖连续检测技术及仪器的研究进展

连续血糖检测对于糖尿病等疾病的诊治意义重大,近年来国内外很多机构都进行了该方面的研究.由于组织液中的葡萄糖浓度与血糖浓度有很好的相关性,基于组织液测量的微创伤血糖检测技术对人体创伤小,且能实现连续的血糖检测,在技术上容易突破,能够较快地在临床上实现,故而受到广泛关注,近年来发展迅猛.按照检测手段的不同,基于组织液测量的微创伤血糖检测技术主要分为皮下植入式和透皮抽取式两种,故本文重点从这两个方面分别阐述了近年来国内外微创伤血糖连续检测技术及仪器的研究进展,并指出了其现阶段存在的主要问题和未来的一些发展方向.     

两通穿孔管消声器声学性能分析

利用试验结果与数值计算结果比较验证FEM预测两通穿孔管消声单元声学性能的正确性,进而运用FEM探讨结构参数对两通穿孔管消声单元声学性能的影响规律。研究结果表明:第二腔、插入管及连接管构成端部共振器,具有良好的低频消声效果;而第一腔中的穿孔段长度对中低频声学性能有较大影响,穿孔率对低频声学性能影响很小、对中频附近频段声学性能影响较大。     

低频超声经皮给药仪设计

利用低频超声波通过介质时对皮肤产生的空化作用、热效应、声微流作用和辐射压等作用能够提供十倍于常规给药方法的持续稳定的渗透率,并且它能够避免首过效应等优点,采用了自动控制和适时控制相结合的智能控制方式,设计了一种基于DS80C320单片机的低频超声经皮给药系统。介绍了它的设计原理、硬件结构,软件流程以及具体实现功能。设计表明,该系统智能化高安全性强,能利用温度、频率和强度等多种因素来促进药物的经皮渗透性。可用于慢性肾功能不全、尿毒症、骨、关节炎和全身性皮肤病的药物经皮渗透,是一套具有实用价值的开发系统。     

可生物降解高分子微针的制作及透皮应用

透皮给药相比于传统的给药方式,具有更多的优势．但是,皮肤的角质层能够阻止外源性物质的侵犯,限制了透皮给药系统的应用．为此,基于微针的透皮给药系统的提出增大了透皮给药系统的应用范围．首先,采用MEM技术制作单晶硅微针．接下来,提出一种新颖、简单而且经济的方法快速制作聚乳酸微针．通过理论分析及有限元分析微针的力学性能,表明微针有足够的强度．体外透皮实验表明,未经微针处理的皮肤,钙黄绿素10h的累计渗透量只有0．17±0．07 μg／cm2;手动进针处理的皮肤只达到4．54±1．17 μg／cm2,比未用微针处理的皮肤增加了30倍;经过进针器处理的皮肤,各个时间点的渗透量均有显著性提高（P〈0．05）,渗透量达到45．37±5．80 μg／cm2,比未用微针处理的皮肤增加了300倍．所有的结果都表明,本实验室制备可降解的聚乳酸微针的方法新颖、快速且经济,而且对于透皮给药系统来说具有很大的潜在价值．     

The Enhanced Iontophoretic Transport of TRH and Its Impedance Study

Abstract

The transdermal drug delivery of iontophoresis provides a noninvasive method for the administration of effective drugs. The enhanced iontophoretic transport of thyrotropin-releasing hormone (TRH), a tripeptide with molecular weight of 362 and a pK_a of 6.2, through an excised rabbit skin has been achieved by in vitro iontophoresis. The results indicate that the steady-state flux of TRH in a diffusion cell is proportional to the current density. In addition, the electrochemical properties of rabbit skin were studied with impedance spectroscopy, and it was found that the skin impedance decreased to a low and stable value with respect to its initial skin impedance while a current was applied through the rabbit skin. This is in good agreement with our experimental results on iontophoretic transport. As compared to passive diffusion, the iontophoresis dramatically increased the transport fluxes of TRH, and ethanol pretreatment further enhanced its iontophoretic transport. A practical implication of these results is that iontophoresis with a chemical permeation enhancer (ethanol pretreatment) can be applied to enhance and control the transdermal delivery of peptides.     

The Enhanced Iontophoretic Transport of TRH and Its Impedance Study

The transdermal drug delivery of iontophoresis provides a noninvasive method for the administration of effective drugs. The enhanced iontophoretic transport of thyrotropin-releasing hormone (TRH), a tripeptide with molecular weight of 362 and a pK_a of 6.2, through an excised rabbit skin has been achieved by in vitro iontophoresis. The results indicate that the steady-state flux of TRH in a diffusion cell is proportional to the current density. In addition, the electrochemical properties of rabbit skin were studied with impedance spectroscopy, and it was found that the skin impedance decreased to a low and stable value with respect to its initial skin impedance while a current was applied through the rabbit skin. This is in good agreement with our experimental results on iontophoretic transport. As compared to passive diffusion, the iontophoresis dramatically increased the transport fluxes of TRH, and ethanol pretreatment further enhanced its iontophoretic transport. A practical implication of these results is that iontophoresis with a chemical permeation enhancer (ethanol pretreatment) can be applied to enhance and control the transdermal delivery of peptides.     

Gelatin Methacryloyl Microneedle Patches for Minimally Invasive Extraction of Skin Interstitial Fluid

The extraction of interstitial fluid (ISF) from skin using microneedles (MNs) has attracted growing interest in recent years due to its potential for minimally invasive diagnostics and biosensors. ISF collection by absorption into a hydrogel MN patch is a promising way that requires the materials to have outstanding swelling ability. Here, a gelatin methacryloyl (GelMA) patch is developed with an 11 × 11 array of MNs for minimally invasive sampling of ISF. The properties of the patch can be tuned by altering the concentration of the GelMA prepolymer and the crosslinking time; patches are created with swelling ratios between 293% and 423% and compressive moduli between 3.34 MPa and 7.23 MPa. The optimized GelMA MN patch demonstrates efficient extraction of ISF. Furthermore, it efficiently and quantitatively detects glucose and vancomycin in ISF in an in vivo study. This minimally invasive approach of extracting ISF with a GelMA MN patch has the potential to complement blood sampling for the monitoring of target molecules from patients.     

Reduced Graphene Oxide Nanohybrid–Assembled Microneedles as Mini‐Invasive Electrodes for Real‐Time Transdermal Biosensing

A variety of nanomaterial‐based biosensors have been developed to sensitively detect biomolecules in vitro, yet limited success has been achieved in real‐time sensing in vivo. The application of microneedles (MN) may offer a solution for painless and minimally‐invasive transdermal biosensing. However, integration of nanostructural materials on microneedle surface as transdermal electrodes remains challenging in applications. Here, a transdermal H₂O₂ electrochemical biosensor based on MNs integrated with nanohybrid consisting of reduced graphene oxide and Pt nanoparticles (Pt/rGO) is developed. The Pt/rGO significantly improves the detection sensitivity of the MN electrode, while the MNs are utilized as a painless transdermal tool to access the in vivo environment. The Pt/rGO nanostructures are protected by a water‐soluble polymer layer to avoid mechanical destruction during the MN skin insertion process. The polymer layer can readily be dissolved by the interstitial fluid and exposes the Pt/rGO on MNs for biosensing in vivo. The applications of the Pt/rGO‐integrated MNs for in situ and real‐time sensing of H₂O₂ in vivo are demonstrated both on pigskin and living mice. This work offers a unique real‐time transdermal biosensing system, which is a promising tool for sensing in vivo with high sensitivity but in a minimally‐invasive manner.     

Investigation into the mechanism by which cyclodextrins influence transdermal drug delivery

The objective of this study was to investigate the mechanism by which hydroxypropyl-beta-cyclodextrin (HPCD) increases transdermal permeation. Hairless mouse skin was pretreated with HPCD solutions for up to 4 h. After removing the HPCD, corticosteroid-containing suspensions were applied and the transdermal flux and skin accumulation of two model drugs were investigated. After pretreatment, changes to the stratum corneum endothermic melting transitions were determined as an indication of HPCD-induced lipid disorganization. Results demonstrated that HPCD pretreatment had no significant effect on the transdermal permeation or skin accumulation of the model corticosteroids. These findings suggest that HPCD functions to enhance the apparent solubility of the drug in the formulation, thus increasing transdermal permeation rather than extracting lipids from the skin.     

Investigation into the Mechanism by Which Cyclodextrins Influence Transdermal Drug Delivery

The objective of this study was to investigate the mechanism by which hydroxypropyl-β-cyclodextrin (HPCD) increases transdermal permeation. Hairless mouse skin was pretreated with HPCD solutions for up to 4 h. After removing the HPCD, corticosteroid-containing suspensions were applied and the transdermal flux and skin accumulation of two model drugs were investigated. After pretreatment, changes to the stratum corneum endothermic melting transitions were determined as an indication of HPCD-induced lipid disorganization. Results demonstrated that HPCD pretreatment had no significant effect on the transdermal permeation or skin accumulation of the model corticosteroids. These findings suggest that HPCD functions to enhance the apparent solubility of the drug in the formulation, thus increasing transdermal permeation rather than extracting lipids from the skin.     

Transdermal penetration of diclofenac in the presence of AAPH-derived peroxyl radicals

In vitro transdermal delivery of diclofenac across pig skin in the presence of AAPH-derived peroxyl radicals (2,2′-azo-bis(2-amidinopropane)dihydrochloride) has been studied. The transdermal absorption of diclofenac was estimated using high-performance liquid chromatography after its incubation in vertical cells. The diclofenac transdermal penetration was highly modified by peroxyl radicals. In the presence of AAPH, lower diclofenac absorption was observed. This effect was inhibited by ferulic acid. This could be explained by diclofenac–peroxyl radical interactions. In the pretreatment skin with AAPH, lower diclofenac absorption was higher than control experiments. This behavior should be considered in the topical administration of pharmaceutical preparations containing diclofenac.     

直管中流体流速对超声波防垢效果的影响

在实验室中采用循环水模拟装置,在相同流体、相同管道、相同温度的条件下,研究了流体流速对超声波防垢效果的影响。结果表明：流体流速变大,造成流体中的实际声强减小,使得超声波防垢率下降,防垢效果变差;当流体流速变大时增大超声波输入功率,防垢率就会上升;超声波频率越高,流体流速对超声防垢效果影响越大。     

Supercritical carbon dioxide extraction of 2,4-dichlorophenol from food crop tissues.

Supercritical fluid extraction with carbon dioxide has been found to be effective for the isolation of residue levels (0.1-1 ppm) of 2,4-dichlorophenol from selected plant tissues. The 2,4-dichlorophenol residues were incompletely extracted with supercritical CO2 alone, since a substantial fraction of the 2,4-dichlorophenol was covalently attached to the plant matrix. An acid pretreatment procedure was developed to partially hydrolyze the plant tissue prior to extraction, releasing the bound 2,4-dichlorophenol residues. Steam distillation showed higher residue levels for field-treated straw samples. This is attributed to the greater degree of hydrolysis inherent in the steam distillation procedure. Supercritical CO2 extraction of field-treated seed samples showed higher levels of 2,4-dichlorophenol residues than did steam distillation. The supercritical fluid extractant was able to solvate 2,4-dichlorophenol residues in the interior of the seed and transport them to the surface for collection. The aqueous medium used in steam distillation was unable to penetrate the hydrophobic seed matrix to the same degree. While the actual extraction time experienced in supercritical fluid extraction was far less than that of steam distillation (45 min vs 6 h, respectively), the total sample preparation time was similar in both methods.