微针与新型经皮给药载体结合的研究进展

经皮给药系统具有给药方便、血药浓度稳定、无首过效应等优点,但皮肤的屏障作用使得药物难以透过皮肤。近年来,出现了很多新型经皮给药的药物载体,如脂质体、醇质体、囊泡等,这些能通过化学方法促进药物的经皮渗透。而微针能穿透皮肤角质层形成微孔通道,通过物理方法促进药物的渗透,将微针与新型经皮给药载体结合能显著提高药物的经皮吸收的速率。本文对微针与新型经皮给药载体结合的最新研究进行了综述,并展望了微针辅助新型药物载体经皮给药的发展前景。     

微针技术的研究进展

微针以微机电系统(m icroelectro-mechani-cal systems,MEMS)技术为基础,在近年来发展迅速。本文主要介绍微针的制备方法,插入皮肤的机制,微针给药的特点以及微针的应用,详细介绍了微针在经皮给药中的应用。由于微针给药可以避免胃肠道对药物的降解作用和肝脏的首过效应等口服给药的缺点,并可消除注射给药时引起的疼痛,随着其发展不断完善,微针给药将会有广阔的应用前景。     

微针经皮给药技术

微针是介于皮下注射和透皮贴剂之间的一种给药方式,利用在皮肤角质层产生的微小孔道来显著增加药物的经皮吸收。综述微针经皮给药技术的研究进展,介绍制造微针的材料和方法、微针的给药方式及其在经皮给药系统中的应用。     

生物可降解微针的研究进展

微针给药是一种新型的经皮给药方式,可在皮肤上创造微米级的药物运输通道,增强皮肤对药物尤其是大分子药物的渗透性,且不会到达神经分布丰富的皮肤深层组织。生物可降解微针是以生物可降解材料为基质制作出的微针,除具有一般微针的优点,其具有的生物可降解特性解决了微针一旦断裂于皮肤内难以处理这一难题。因此生物可降解微针有望成为经皮给药的理想载体。本文对生物可降解微针的特点、制作方法、基质的选择、在经皮给药系统中的应用以及存在的问题等进行了概述。     

微针在儿童经皮递药中的研究进展

与传统的口服和肠外给药途径相比,经皮给药系统作为一种非侵入性替代方法非常有吸引力。特别对于儿童患者,它有助于克服该群体特有的问题,如吞咽困难、口服制剂的适口性以及与针头相关的恐惧和疼痛。然而,儿童的皮肤屏障功能有效地限制了药物的经皮吸收。微针可突破皮肤最外层的角质层,增加经皮给药的药量。过去几十年,以微针为基础药物输送系统的研究取得了显著进展。与微针相关的研究论文呈指数级激增。本文概括了微针的分类及特点,讨论了微针在儿童经皮递药中的研究进展,最后对微针介导的儿童经皮递药的未来前景进行了简要展望。     

不锈钢微针经皮给药的研究

目的：将不锈钢微针阵列应用于经皮给药。考察离体大鼠皮肤经不同针形微针预处理相同时间、相同针形微针预处理不同时间后，模型药物鬼臼毒素经大鼠皮肤的透皮能力。方法：微针预处理大鼠皮肤后，用改进的Franz扩散池研究鬼臼毒素对皮肤的透皮速率。高效液相色谱法测定鬼臼毒素的含量。结果：皮肤经微针预处理后进行鬼臼毒素透皮，其透皮速率比未经微针处理时有明显提高。三角形微针、梯形微针、矛形微针对鬼臼毒素的促渗能力依次增强；三者所引起的鬼臼毒素在皮肤中的滞留量有显著差异。同种针形微针预处理皮肤时间越长，鬼臼毒素的透皮速率越大；但微针预处理时间对皮肤中的药物滞留量无显著影响。结论：微针用于药物经皮给药时，微针针形、微针的预处理时间对药物的经皮渗透具有重要影响。     

微针经皮给药应用的新进展

微针有助于改善患者的用药依从性,提高药物的生物利用度.近年来,微针在疫苗接种、蛋白质和多肽给药、DNA给药、皮肤美容、眼科用药、局部麻醉、微量取样等领域均有应用.微针在胰岛素给药和局部麻醉中的研究已进入临床试验阶段,在皮肤美容、疫苗接种和蛋白质给药方面已有上市产品.     

微针新型经皮给药新技术的应用及研究进展

药物通过皮肤表面进入体内,并通过循环发挥其药效就是所谓的经皮给药,但是经皮给药这种给药方式有一个很大的障碍——皮肤。如何克服皮肤的障碍,促进药物的渗透是药剂研究者一直以来备受关注的。通过经皮给药的药物载体有很多,如醇质体、传递体、微乳、非离子囊泡等,这些都是化学促渗透的方法。本文主要对一种新型的物理促渗透方法进行介绍,经过大量文献资料的查阅,对微针这种经皮给药新技术的应用和研究的最新进展进行阐述。     

微针在经皮给药及经皮疫苗转运中的应用

作为一种高效、无痛、精确、便利的给药系统，微针可显著促进药物及疫苗的经皮转运，显示其在经皮给药领域的良好应用前景。     

难溶性多西紫杉醇的溶解微针制备及体外评价

目的:制备一种用于透皮给药的负载多西紫杉醇(DTX)的溶解微针,并进行体外评价。方法:考察不同材料及配方制备DTX溶解微针(DTX-MN),通过外观和力学性能指标对微针进行表征,测定微针针头载药量。使用猪皮肤考察微针溶解性能。剥离小鼠腹部皮肤,进行体外透皮吸收研究,初步考察DTX-MN给药后的皮肤药代动力学。结果:成功制备了针头完整、力学性能良好的DTX-MN,最佳工艺得到的微针针头载药量为(14.81±4.20)μg (n=5),微针能完整插入皮肤穿透角质层屏障,且在10 min内完全溶解。体外透皮实验显示,DTX-MN的初始透皮速率和累积透皮通量都高于药物溶液组,相比溶液组,DTX-MN在24 h后累积渗透量提高了3.27倍,其释放机制符合Fickian扩散。结论:制备的DTX-MN有良好的穿刺皮肤的性能,能够显著促进DTX的透皮递送,该类微针有望促进DTX的浅表皮肤递送,具有潜在的临床应用价值。     

Microneedles: an emerging transdermal drug delivery system

Objectives One of the thrust areas in drug delivery research is transdermal drug delivery systems (TDDS) due to their characteristic advantages over oral and parenteral drug delivery systems. Researchers have focused their attention on the use of microneedles to overcome the barrier of the stratum corneum. Microneedles deliver the drug into the epidermis without disruption of nerve endings. Recent advances in the development of microneedles are discussed in this review for the benefit of young scientists and to promote research in the area. Key findings Microneedles are fabricated using a microelectromechanical system employing silicon, metals, polymers or polysaccharides. Solid coated microneedles can be used to pierce the superficial skin layer followed by delivery of the drug. Advances in microneedle research led to development of dissolvable/degradable and hollow microneedles to deliver drugs at a higher dose and to engineer drug release. Iontophoresis, sonophoresis and electrophoresis can be used to modify drug delivery when used in concern with hollow microneedles. Microneedles can be used to deliver macromolecules such as insulin, growth hormones, immunobiologicals, proteins and peptides. Microneedles containing ‘cosmeceuticals’ are currently available to treat acne, pigmentation, scars and wrinkles, as well as for skin tone improvement. Summary Literature survey and patents filled revealed that microneedle‐based drug delivery system can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional transdermal techniques.     

Heterogeneity in skin treated with low-frequency ultrasound

Recent experimental evidence using colored, fluorescent permeants suggests that skin treated with low-frequency sonophoresis (LFS) is perturbed in a heterogeneous manner. Macroscopic and microscopic visualization studies, topical penetration studies, transdermal permeability studies, and skin electrical resistivity measurements have shown that discrete domains, referred to as localized transport regions (LTRs), which are formed during LFS treatment of the skin, possess greatly reduced barrier properties, and therefore exhibit increased permeant skin penetration, compared to the surrounding regions of LFS-treated skin. The transformation of LTR formation from a heterogeneous to a homogeneous phenomenon has the potential benefit of increasing the maximum level of transdermal permeability or of reducing the area of skin required to deliver a desired dose of drug transdermally. Future studies, aimed at elucidating both the mechanisms of LTR formation and the limits of nondamaging formation of LTRs in the skin, are required to incorporate these proposed improvements to enhance the efficacy and practical utility of low-frequency sonophoresis.     

Status of terpenes as skin penetration enhancers

Since its introduction, transdermal drug delivery has promised much but, in some respects has still to deliver on that initial promise, due to inherent limitations imposed by the percutaneous route. The greatest obstacle for transdermal delivery is the barrier property of the stratum corneum. Many approaches have been employed to breach the skin barrier, of which, the most widely used one is that of chemical penetration enhancers. Of the penetration enhancers, terpenes are arguably the most highly advanced and proven category and are classified as generally regarded as safe (GRAS) by the Food and Drug Administration. This paper presents an overview of the investigations on the feasibility and application of terpenes as sorption promoters for improved delivery of drugs through skin.     

Microneedles: a valuable physical enhancer to increase transdermal drug delivery

Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Recently, the use of micron-scale needles in increasing skin permeability has been proposed and shown to dramatically increase transdermal delivery. Microneedles have been fabricated with a range of sizes, shapes, and materials. Most in vitro drug delivery studies have shown these needles to increase skin permeability to a broad range of drugs that differ in molecular size and weight. In vivo studies have demonstrated satisfactory release of oligonucleotides and insulin and the induction of immune responses from protein and DNA vaccines. Microneedles inserted into the skin of human subjects were reported to be painless. For all these reasons, microneedles are a promising technology to deliver drugs into the skin. This review presents the main findings concerning the use of microneedles in transdermal drug delivery. It also covers types of microneedles, their advantages and disadvantages, enhancement mechanisms, and trends in transdermal drug delivery.     

Passive transdermal drug delivery systems

The skin has evolved as a formidable barrier against invasion by external microorganisms and against the prevention of water loss. Notwithstanding this, transdermal drug delivery systems have been designed with the aim of providing continuous controlled delivery of drugs via this barrier to the systemic circulation. There are numerous systems now available that effectively deliver drugs across the skin. These include reservoir devices, matrix diffusion-controlled devices, multiple polymer devices, and multilayer matrix systems. This review article focuses on the design characteristics and composition of the main categories of passive transdermal delivery device available. Mechanisms controlling release of the active drug from these systems as well as patch size and irritation problems will be considered. Recent developments in the field are highlighted including advances in patch design as well as the increasing number of drug molecules now amenable to delivery via this route. From the early complex patch designs, devices have now evolved towards simpler, matrix formulations. One of the newer technologies to emerge is the delivery-optimized thermodynamic (DOT) patch system, which allows greater drug loading to be achieved in a much smaller patch size. With the DOT technology, drug is loaded in an acrylic-based adhesive. The drug/acrylic blend is dispersed through silicone adhesive, creating a semi-solid suspension. This overcomes the problem with conventional drug-in-adhesive matrix patches, in which a large drug load in the adhesive reservoir can compromise the adhesive properties or necessitate a large patch size. Transdermal drug delivery remains an attractive and evolving field offering many benefits over alternative routes of drug delivery. Future developments in the field should address problems relating to irritancy and sensitization, which currently exclude a number of therapeutic entities from delivery via this route. It is likely that further innovations in matrix composition and formulation will further expand the number of candidate drugs available for transdermal delivery.     

经皮给药的研究进展

药物的透皮给药主要受到皮肤障碍、药物的分子量和亲水/油性等因素的影响.利用物理和化学方法,同时,辅以载体方法可有效提高药物(尤其是生物大分子药物和复方中药)经皮给药效率.随着透皮给药的不断发展改进,经皮给药系统一定会发挥更大的潜力.     

Potential and problems of developing transdermal patches for veterinary applications

A new frontier in the administration of therapeutic drugs to veterinary species is transdermal drug delivery. The primary challenge in developing these systems is rooted in the wide differences in skin structure and function seen in species ranging from cats to cows. The efficacy of a transdermal system is primarily dependent upon the barrier properties of the targeted species skin, as well as the ratio of the area of the transdermal patch to the species total body mass needed to achieve effective systemic drug concentrations. A drug must have sufficient lipid solubility to traverse the epidermal barrier to be considered for delivery for this route. A number of insecticides have been developed in liquid ‘pour-on’ formulations that illustrate the efficacy of this route of administration for veterinary species. The human transdermal fentanyl patch has been successfully used in cats and dogs for post-operative analgesia. The future development of transdermal drug delivery systems for veterinary species will be drug and species specific. With efficient experimental designs and available transdermal patch technology, there are no obvious hurdles to the development of effective systems in many veterinary species.     

新型透皮给药载体--传递体研究进展

概述新型透皮给药载体——传递体研究的特点、组成及制备方法、穿透动力学以及研发设计中应注意的问题。传递体以其自身的特点与技术，将在不久的将来研发出各种传递体皮肤外用制剂。