树状大分子用于药物载体的研究进展

树状大分子(Dendri mers)是指具有树状结构,高度支化,由活性中心、表面功能基团及连接二者的支化链段构成的超大分子。支化链段是按几何学规则进行的重复,重复单元导致产生一系列同心层,称为代数(Generations)[1]。Dendri mers具有水溶性好、生物相容性好、单分散性、生物降解性、表面有较多易被修饰的活性基团等特点,这使其在药物载体的应用领域具有较好前景。现对其用于抗肿瘤药阿霉素、甲氨蝶呤(MTX)、米托蒽醌的药物载体的研究较多。而有关Dendri mers载药机制的研究及作为产品开发也已成为药剂学领域发展的热点之一。为此,笔者就De…     

新型基因载体-聚酰胺-胺树状大分子聚合物

利用重组DNA技术进行疾病预防和治疗是近几年来的研究热点,如何提高重组DNA的转染效率一直是研究的难题之一,新型阳离子多聚物--聚酰胺-胺型树状大分子(Starburst PAMAM dendrimers,PAMAM-D)的出现为解决现存的难题带来希望.PAMAM-D最早由美国人Tomalia于1985年合成,目前已广泛应用于各个领域:药物载体、废水处理、催化剂、光电传感、基因载体等.由于PAMAM-D具有对称的刚性球体结构,表面带有大量正电荷,容易与带负电荷的核酸形成复合物,故作为基因载体具有许多优于其他现有转染试剂的优良特性.本文主要介绍了PAMAM-D的结构、性质、应用以及作为基因载体的优越性,并对今后的研究方向进行了概述.     

树状大分子在生物医药领域中的应用

大量的末端官能团、紧密且精确控制的分子结构是树状大分子所具有的独特性质。这些特性使得树状大分子应用于生物医学领域，例如在分子水平上功效的增强，使药物在局部产生高浓度、分子标记及作为探针组件等。本文简要介绍树状大分子在这一领域的新动态，特别是树状大分子在诊断和治疗中的应用。在诊断方面，Gd^3 与树状大分子复合物可用作核磁共振成像造影剂，DNA树状大分子能用于常规的高效功能性基因检测及DNA生物传感器。在治疗方面，树状大分子可作为控释药物的载体、基因转染剂和硼中子俘获治疗剂等。研究表明，树状大分子还具有抗菌活性。     

脂质体作为生物大分子载体的研究进展

对脂质体作为生物大分子载体，即作为基因物质，生物药物的载体，新型疫苗佐剂和载体，以及生物药物脂质体的给药途径进行了讨论。     

大分子胶束作为药物载体的应用

大分子胶束可以作为疏水性药物和核酸、蛋白等药物的载体，并具有高效、长效、安全性和靶向性等特点，是一种很有发展前景的药物载体。现主要从大分子胶束的特点、载药机制、形成材料、制备方法、包载的药物及其靶向性方面综述大分子胶束作为药物载体的应用。     

聚酰胺-胺树状大分子作为药物载体的体外增溶、缓释试验

目的:考察以聚酰胺-胺树状大分子(PAMAM)作为喹诺酮类药物载体在增溶、缓释方面的作用。方法:根据文献合成PAMAM,并作结构分析;以巴洛沙星为模型药物,检测不同代数不同浓度的PAMAM对巴洛沙星的增溶作用;同时用不同代数的PAMAM与巴洛沙星复合,检测PAMAM对巴洛沙星体外释放的影响,以及在水及模拟肠液中的释放情况。结果:巴洛沙星在水中溶解度约为1.5g·L-1,完全释药时间约为4h。随着PAMAM代数和浓度的增加巴洛沙星溶解度增加(2～5.25g·L-1),PAMAM与巴洛沙星复合物在水中24h释放80%,在模拟肠液中72h释放73%。结论:PAMAM对巴洛沙星具有增溶、缓释作用,有可能促进其制成具有缓释作用的溶液剂或注射剂。     

树状大分子：一类新型的纳米容器和输送装置

与传统的线性高聚物相比，树状大分子和超支化高聚物是一类相关的具有独特分子结构及大小的新型材料。本文详述了近年来这些高聚物作为新型聚合物输送体系应用方面的重要进展。超支化的药物输送装置领域目前正在快速发展成熟，同时由于在药物-包合物系统的研究中的重大发现而备受关注。本文也介绍了具有理想的超支化结构的树状大分子在主体-客体化学中的应用。     

促进大分子药物跨血脑屏障转运多功能载体的研究进展

血脑屏障(Blood Brain Barrier，BBB)在防止异物入侵，保护脑功能正常方面起着非常重要的作用。促进药物特别是大分子药物跨过BBB入脑是脑疾病药物治疗学和脑药发展的重要研究领域之一。本文就近年促进药物跨BBB转运体系的研究进展作综述性介绍。     

聚乙二醇化聚酰胺-胺树状大分子的合成及作为基因载体的研究

目的研究聚乙二醇(polyethylene glycol,PEG)化聚酰胺-胺树状大分子(polyamidoamine dendrimer,PAMAM)的理化性质及其作为质粒DNA载体。方法用1H-NMR考察PAMAM-PEG的化学结构;用琼脂糖凝胶电泳法、圆二色谱法和透射电镜法考察复合物的形成;用动态光散射法测定复合物的粒径和zeta电位;用MTT法测定复合物的毒性;用萤光素酶报告基因的表达表征复合物的转染效率。结果结果表明,载体化合物合成成功,PEG修饰度为9%;琼脂糖凝胶电泳结果表明,在N/P比大于2时,复合物能阻滞DNA的电泳;圆二色谱、透射电镜结果表明复合物已经形成,其形态规整,呈球形。随着N/P比的增加,复合物的粒径减小,zeta电位升高;MTT结果表明复合物的细胞毒性小;萤光素酶实验结果表明复合物的转染效率高。结论作为DNA载体,PAMAM-PEG的细胞毒性小、转染效率高,具有很大的研究前景。     

Nanostructured lipid carriers system: Recent advances in drug delivery

Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.     

脂质体递药系统的临床研究进展

本文将脂质体递药系统按结构、组成和功能分成普通脂质体、多囊脂质体、长循环脂质体、热敏脂质体和免疫脂质体5类，分别介绍其应用和临床研究进展。     

作用于新生儿Fc受体药物递送系统研究进展

新生儿Fc受体(FcRn)最早发现是母体抗体传递给胎儿和新生儿的膜表面蛋白,后来也证明在成人体内也在多器官、多组织中终生表达,其维持着免疫球蛋白G和血清白蛋白在机体中的长循环和动态平衡,在固有免疫和适应性免疫调节中发挥着极为重要的作用。在现代生物制药研究中, FcRn是良好的药物递送靶点,也是目前研究的热点。本文简述了FcRn的基本生物学性质和作用机制,以及目前常用的FcRn的药物载体设计策略,特别是对于延长半衰期、靶向输送、跨生物膜及抗原递呈等多方面的功能应用进行展望。FcRn在不同组织内的分布和生物学功能,为未来基于FcRn的新型药物递送系统研究和免疫治疗方面等提供更广阔的思路。     

Recent advances in intraocular drug delivery systems

Vitreoretinal diseases are refractory to both topical and systemic pharmacological approaches because of specific environment of the eye. That is, the cornea, the sclera, nasolacrimal drainage of tears, frontward stream of aqueous humor, blood-aqueous barrier, and blood-retinal barrier strictly limit penetration and diffusion of drug into the retina. However, recent advances in intraocular drug delivery systems (DDS) have enabled drug to be delivered effectively into the eye. Clinically successful or promising cases involve non-biodegradable implants and inserts, biodegradable inserts and microparticles, intravitreal or sub-Tenon's injection of triamcinolone acetonide, and a photodynamic therapy (PDT) with verteporfin, a photosensitizer. More recently, a variety of pharmacological challenges to treat exudative age-related macular degeneration and macular edema are proceeding into clinical trials, as soon as anti-vascular endothelial growth factor (anti-VEGF) therapies have been proved to be effective by repeated intravitreal injections. In the near future, DDS must be required not only to develop a new treatment modality but also to improve efficacy and/or reduce injection numbers of currently available drugs. Here we introduce controlled release of drug and discussion of recent patents with biodegradable or non-biodegradable implants and drug targeting by modification of systemically administered drug.     

皮肤真菌病新型局部给药系统研究进展

皮肤真菌病是易发病、易传染、易复发的疾病,严重影响患者生活质量。局部给药制剂直接作用于病变部位,使用方便,患者顺应性好,是皮肤真菌病临床治疗的首选。以脂质体、醇质体、微乳和脂质纳米粒等为代表的新型给药系统,可以提高药物的渗透性,减小药物透过,使其在皮肤局部蓄积,从而能够增强疗效、缩短疗程和减少不良反应,使皮肤真菌病的局部治疗更具有应用前景。本文综述了近年来国内外皮肤真菌病新型局部给药系统的研究进展。     

Recent advances in inorganic nanoparticle-based drug delivery systems

Drug delivery systems, designed to enhance drug efficacy and reduce their adverse effects, have evolved accompanied by the development of novel materials. Nanotechnology is an emerging scientific area that has created a variety of intriguing inorganic nanoparticles. In this review, we focus on the feasibility of inorganic nanoparticles, including iron oxide nanoparticles, gold nanoparticles, fullerenes and carbon nanohorns, as drug carriers, and summarize recent advances in this field.     

Recent advances in electrospun for drug delivery purpose

Abstract

Electrospun, an advanced technology, has been successfully employed for fibre production and offers many merits in novel drug delivery systems (DDSs). In recent years, electrospun has gained significant attention and attraction of the scientists in soaring numbers. This technology is superior to other technologies in fabricating the fibres which range from micrometers to manometers scale. The selection of appropriate polymers, electrospun processes and electrospun parameters play important roles in controlling the drug release while, treating serious illness. Besides, electrospraying process has similar characteristics to the electrospun and is presented briefly here. Further, in vivo and in vitro evaluations of the electrospun nanofibers are comprehensively discussed. In addition, the electrospun nanotechnology has been exploited to design drug release systems, investigate drug’s pharmacokinetics and further develop DDS. The electrospun nanofibers improve bioactivity of various types of drugs including water-insoluble, soluble, anticancer and antibacterial drugs and genetic materials. In the end, the prospects and challenges in the process of designing drug-loaded electrospun nanofibers are discussed in detail.     

Recent advances in the role of supramolecular hydrogels in drug delivery

Introduction: Supramolecular hydrogels, formed by noncovalent crosslinking of polymeric chains in water, constitute an interesting class of materials that can be developed specifically for drug delivery and biomedical applications. The biocompatibility, stimuli responsiveness to various external factors, and powerful functionalization capacity of these polymeric networks make them attractive candidates for novel advanced dosage form design.

Areas covered: This review summarizes the significance of supramolecular hydrogels in various biomedical and drug delivery applications. The recent advancement of these hydrogels as potential advanced drug delivery systems (for gene, protein, anticancer and other drugs) is discussed. The importance of these hydrogels in biomedical applications, particularly in tissue engineering, biosensing, cell-culture research and wound treatment is briefly described.

Expert opinion: The use of supramolecular hydrogels in drug delivery is still in very early stages. However, the potential of such a system is undeniably important and very promising. A number of recent studies have been conducted, which mainly focus on the use of cyclodextrin-based host–guest complex as well as other supramolecular motifs to form supramolecular hydrogels for delivery of various classes of drugs, therapeutic agents, proteins and genes. However, there are still plenty of opportunities for further development in this area for drug delivery and other biomedical applications.     

Recent advances in testing of microsphere drug delivery systems

ABSTRACT

Introduction: This review discusses advances in the field of microsphere testing.

Areas covered: In vitro release-testing methods such as sample and separate, dialysis membrane sacs and USP apparatus IV have been used for microspheres. Based on comparisons of these methods, USP apparatus IV is currently the method of choice. Accelerated in vitro release tests have been developed to shorten the testing time for quality control purposes. In vitro-in vivo correlations using real-time and accelerated release data have been developed, to minimize the need to conduct in vivo performance evaluation. Storage stability studies have been conducted to investigate the influence of various environmental factors on microsphere quality throughout the product shelf life. New tests such as the floating test and the in vitro wash-off test have been developed along with advancement in characterization techniques for other physico-chemical parameters such as particle size, drug content, and thermal properties.

Expert opinion: Although significant developments have been made in microsphere release testing, there is still a lack of guidance in this area. Microsphere storage stability studies should be extended to include microspheres containing large molecules. An agreement needs to be reached on the use of particle sizing techniques to avoid inconsistent data. An approach needs to be developed to determine total moisture content of microspheres.     

Toxicogenomics of drug delivery systems: Exploiting delivery system-induced changes in target gene expression to enhance siRNA activity

Synthetic siRNAs are typically formulated with drug delivery systems (DDS) that improve cellular uptake for optimal gene silencing activity. Here, we show that two PAMAM dendrimer DDS, differing only in their structural architecture, elicit many different gene expression changes in human cells including opposing effects on the expression of epidermal growth factor receptor (EGFR), a gene targeted for silencing by siRNA. Despite providing similar improvements in siRNA uptake, these two formulations led to a ～10-fold variation in anti-EGFR siRNA activity. These data show that gene expression changes induced by DDS, separate from their ability to enhance cell uptake, determine ‘apparent’ siRNA potency and thus offer the possibility of tailoring delivery system-siRNA combinations for additive or synergistic effects on gene silencing.