纳米微球药物缓释技术

纳米微球作为药物载体被越来越多地应用于医药领域,这一技术得到研究者的广泛重视。目前已有多种纳米微球制剂投入临床使用。纳米微球的深入研究具有重要的意义。我们概述了近年来纳米微球的研究及应用情况,展望了纳米微球药物载体缓释技术的应用前景及需要解决的问题。     

海藻酸钠壳聚糖微球作为药物载体的研究进展

海藻酸钠壳聚糖微球是具有生物粘附性且能结合和传递大分子药物的天然高分子材料,且在生物医学领域具有广阔应用前景的药物载体。它具有生物黏附性、生物相容性、生物可降解性、对人体无毒性且能够结合和传递大分子药物的天然高分子材料。海藻酸钠壳聚糖微球作为载药微球具有提高药物的生物利用度、延长药物的作用时间等优点。国内外近些年已将其应用于药剂学领域,以及将其作为药物载体经微球化与药物结合形成给药系统的研究也在逐步开展并取得了较多成果。本文主要阐述海藻酸钠壳聚糖微球的主要生物特性、作用特点及其在医学领域中应用的研究进展,并对其应用前景进行探讨。     

新型药物递送系统研究进展

药物递送系统系采用多学科的手段将药物有效地递送到目的部位,从而调节药物的代谢动力学、药效、毒性、免疫原性和生物识别等.与传统制剂相比,药物递送系统可以提高药物的稳定性,减少药物的降解;减轻药物的毒副作用;提高药物的生物利用度;维持稳定有效的血药浓度,避免血药浓度波动;可以提高靶区药物浓度.目前已发展建立了多种类型的新型药物递送系统,其研究投入和市场份额持续快速增长,推动着全球医药产业的发展.本文主要就军事医学科学院毒物药物研究所近年来研究内容纳米靶向脂质体、新型纳米药物递送系统、长效缓释微球、口服缓控释制剂和干粉吸入制剂等研究进展作一综述.     

乳酸菌制剂的研究进展

乳杆菌（Lactic acid bacteria）是无芽胞的厌氧或兼性厌氧的G^＋性菌,存在于人类和其他动物体内（肠道、鼻腔和阴道黏膜）以及环境中（以植物为主）的一类非常重要的微生物,对维持胃肠道的生理功能具有重要作用。自从1907年METCHNIKOFF发现乳酸菌能够抑制腐败菌生长和增强机体免疫力后,乳酸菌对机体免疫功能及其他应用受到各界的广泛关注。     

QCM监测不同浓度肌力药物作用下乳鼠原代心肌细胞的粘弹性响应

采用石英晶体微天平(QCM)非侵入式实时监测乳鼠原代心肌细胞于金晶体电极上的动态黏附响应与不同浓度肌力药物下的粘弹性响应。在乳鼠原代心肌细胞黏附铺展于金晶体电极表面后,加入不同浓度的正性肌力药物异丙肾上腺素与负性肌力药物维拉帕米,监测QCM频率(F)以及动态电阻(R)的实时变化,采用粘弹性指数CVI(CVI=ΔR/ΔF)表征细胞的粘弹性变化,并通过光学显微镜观察药物作用下细胞的形态变化。结果表明:随着异丙肾上腺素浓度的增加,药物引起的QCM频率下降、电阻增加与CVI增大的幅度均增大;光学显微镜下观测到细胞收缩,符合CVI变大、细胞变硬的响应;随着维拉帕米浓度的增加,药物引起的QCM频率升高、电阻下降与CVI减小的幅度均增大;光学显微镜下观测到细胞舒张,符合CVI变小、细胞变软的响应。说明QCM与原代心肌细胞结合作为心血管药物筛选细胞模型与工具有很大的应用前景。     

内质网靶向纳米药物的研究进展

内质网作为真核细胞内极为重要的细胞器,在生物大分子合成与加工、物质转运、离子稳态维持、信号转导、细胞器间物质与信号交流等诸多方面发挥关键作用,其功能异常与癌症、自身免疫疾病、病原微生物感染、神经退行性疾病、糖尿病等诸多重大疾病紧密相关.随着纳米技术的不断发展,内质网靶向纳米药物的开发与应用逐渐成为生物工程、纳米医学、材...     

丝素微球的制备方法研究进展

丝素蛋白因其特殊的物理化学性质,为制备不同形态的材料提供了依据;丝素蛋白也因其良好的生物相容性、生物降解性为生物材料应用提供了重要的临床选择。本文综述了国内外学者对丝素微球的制备方法的探究,包括乳化法、喷雾干燥法、层流射流技术以及自组装方法,并比较了各种制备方法的优缺点。此外,本文还介绍了丝素微球在药物缓释领域中的应用进展,并提出了几个针对制备丝素微球亟需解决的问题。     

改善蛋白质药物PELA控释微球释放性能的研究

开展了以乙酸乙酯(EA)与二氯甲烷(MC)的混合溶液为有机溶剂、以单甲氧基聚乙二醇-聚-DL-乳酸(PELA)为膜材的W／O／W复乳-分步固化法制备蛋白质药物控释微球的研究。为解决微球突释率高、且突释后的释药速度缓慢的问题,实现后期快速释放,以溶菌酶为模型蛋白,重点考察了膜材组成、内水相体积以及外水相盐浓度对微球释药速率的影响。结果表明,当外水相盐浓度增大至1.5％时可将释放率由22％提升至45％,是一种较好的加快微球释药速率的途径,因此可通过选择适当的外水相盐浓度,达到所期望的药物释药速率。     

磁性微球的制备及在生物分离应用中的研究进展

磁性微球是一类新型的功能材料,在生物医学工程、细胞生物学和环境工程具有广泛的应用。本文从磁性微球的结构、特性和制备方法进行了探讨,并详细介绍了磁性微球在细胞分离、蛋白质以及核酸的制备纯化领域中的应用。     

高分子药物缓释用壳聚糖微球的制备

本文采用了先交联制备可溶胀的壳聚糖载体微球,后将模型高分子药物以被动吸咐方式担载在溶胀的微球内的两步法,制备缓释高分子药物微球,避免了高分子药物接触有机试剂引起的活性损失。     

Multichannel quartz crystal microbalance array: Fabrication,evaluation, application in biomarker detection

A multichannel quartz crystal microbalance array (MQCM) with three pairs of gold electrodes was fabricated for detection of two biomarkers: acetone and nitric oxide (NO). The gold electrodes were deposited symmetrically on an AT-cut 10 MHz circular quartz plate using photolithography, sputtering, and lift-off technologies. The effect of gold layer thickness on MQCM performance was investigated and the optimized thickness was 101 nm. The simulation values of the electric parameters C₀, C_q, L_q, and R_q in the Butterworth–Van Dike equivalent circuit for the MQCM device were 97 pF, 1.3 pF, 1.05 mH, and 9.8 Ω, respectively. Simulation values were in the theoretical range, which indicated that the fabricated MQCM device had good resonance performance. Two types of nanocomposites, titanium dioxide–multiwalled carbon nanotubes and cobalt (II)phthalocyanine–silica, were synthesized as sensing materials. The sensing mechanism is based on coordination adsorption of target molecules onto the sensing material, resulting in a resonant frequency shift of modified QCM sensor. A linear range from 4.33 to 129.75 ppmv for acetone was obtained and one from 5.75 to 103.45 ppbv for NO.     

Lyotropic liquid crystal as a real-time detector of microbial immune complexes

AIMS: To design a simple method for the detection of microbe-immune complexes exploiting the optical and elastic properties of a biocompatible liquid crystalline material. METHODS AND RESULTS: Aqueous solution of disodium cromoglycate (DSCG), a lyotropic chromonic liquid crystal (LCLC), was aligned in a glass cell so as to be optically dark in polarized light. Immune complexes of at least three to four organisms altered the DSCG alignment such that polarized light was subsequently transmitted to reveal the presence of pathogens as optically bright regions around the immune complexes. CONCLUSIONS: This work describes the first method to detect viable micro-organisms in real time using LCLC. SIGNIFICANCE AND IMPACT OF THE STUDY: This technique provides a powerful tool for the detection of microbes in minutes, exploiting the optical and elastic properties of LC.     

Interfacial layering and orientation ordering of ionic liquid around single-walled carbon nanotube: a molecular dynamics study

Single-walled carbon nanotubes (SWNTs) tend to aggregate to heavily tangled bundles due to the strong van der Waals attraction. Ionic liquids (ILs) are a kind of newly proposed solvents in which SWNT can be physically well dispersed. In this article, the cylindrical interface has been investigated by molecular dynamics simulation between IL of 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF4]) and an infinite long armchair (6,6) SWNT. The highly ordered structure of the cations and anions is elucidated by the simulation results. Two evident dense layers are found for both the cations and anions along the surface normal direction of the SWNT. In addition, we have observed two different orientation patterns of the cations in the first layer. In sublayer 1A, which is the nearest to the surface, the imidazolium rings of the cations prefer to be parallel to the surface, with a slight tilt angle less than 15°. In sublayer 1B, they tend to be perpendicular to the surface, with their butyl chains appearing in sublayer 1A. The [BF₄]^?  anions are found to cling to the nanotube surface with three fluoride atoms, also indicating a highly ordered orientation. The simulation results in this work provide a clue to understand the stabilisation and dispersion of SWNT bundles in ILs.     

Structure of a complex between yeast hexokinase A and glucose: II. Detailed comparisons of conformation and active site configuration with the native hexokinase B monomer and dimer

Detailed comparison of the refined crystal structures of the hexokinase A: glucose complex (HKA · G) and native hexokinase B shows that, in addition to the 12 ° rotation of one lobe of the enzyme relative to the other as described previously (Bennett & Steitz, 1978) there are small systematic differences in the conformation of the polypeptide backbones of the two structures adjacent to the glucose binding site and crystal packing contacts. In the HKA · G complex, the cleft between the two lobes of the hexokinase molecule is narrowed, substantially reducing the accessibility of the active site to solvent. The HKA · G structure suggests specific contacts with a bound glucose molecule that cannot form in the more open native structure. The closed conformation of the HKA · G complex can be formed by either subunit in the heterologous dimer configuration of hexokinase B (Anderson et al. 1974); new or different interactions between subunits, or with ligands bound to the intersubunit ATP site, may be made when the upper subunit of the dimer is in the closed conformation and may contribute to the cooperative interactions observed in the crystalline dimer and in solution.     

The bioelectronic nose and tongue using olfactory and taste receptors: Analytical tools for food quality and safety assessment

Food intake is the primary method for obtaining energy and component materials in the human being. Humans evaluate the quality of food by combining various facets of information, such as an item of food's appearance, smell, taste, and texture in the mouth. Recently, bioelectronic noses and tongues have been reported that use human olfactory and taste receptors as primary recognition elements, and nanoelectronics as secondary signal transducers. Bioelectronic sensors that mimic human olfaction and gustation have sensitively and selectively detected odor and taste molecules from various food samples, and have been applied to food quality assessment. The portable and multiplexed bioelectronic nose and tongue are expected to be used as next-generation analytical tools for rapid on-site monitoring of food quality. In this review, we summarize recent progress in the bioelectronic nose and tongue using olfactory and taste receptors, and discuss the potential applications and future perspectives in the food industry.     

Kinetics of drug-DNA interaction. Dependence of the binding mechanism on structure of the ligand

Kinetic and equilibrium studies of the binding of several phenanthridines and acridines to DNA have been performed to investigate the physical processes underlying the direct ligand transfer mechanism of drug-DNA interaction· Substitution of the 6-phenyl ring of dimidium with a p-carboxyl residue, or complete removal of either the 6-substituent or the 3-amino group, does not prevent the phenanthridine chromophore from transferring directly between binding sites. Loss of the aromatic ring increases association rate constants three- to ninefold and enhances dissociation rates by factors of up to 12; the rates of direct transfer and dissociation from site 1 are the most perturbed. The presence of a phenyl ring stabilizes the site 1 complex and lowers the binding constant to site 2. Introduction of the p-carboxyl group does not affect the equilibrium distribution of bound forms but produces equivalent increases (2·5-fold) in forward and reverse rate constants for binding to site 1 and for the direct transfer step. The 3-amino group greatly stabilizes the site 1 complex. Its removal accelerates all kinetic processes except for the reverse transfer step; the transfer rate is enhanced 25-fold and binding to site 2 is increased 12-fold. The dissociation rate from site 1 rises by a factor of 45 and that from site 2 by a factor of 5·8.10-Methyl-9-aminoacridine binds via the direct transfer pathway with rate and equilibrium constants similar to those of the 3-desamino derivative of ethidium. This compound provides the first fully characterized example of an acridine that utilizes bimolecular transfer. By contrast, rivanol (6,9-diamino-2-ethoxyacridine) interacts with DNA via a two-step sequential mechanism analogous to that seen with proflavine, yet its intrinsic association constant is three times higher. This results from tighter ‘external’ attachment to the helix, together with a decrease in equilibrium constant for the insertion step, which is markedly slower than that of proflavine. There appears to be a simple relation between the apparent enthalpy of binding and the number of extracyclic amino substituents on the intercalating chromophore.We propose that the two bound forms that participate in direct ligand transfer represent molecules intercalated via one or other of the grooves of DNA, and that the transfer pathway corresponds to exchange of drug between the wide groove of one helix and the narrow groove of another. The ability to form strongly bound complexes at the surface of the helix appears to play a major role in determining the mechanism of ligand binding.