新型药物载体-醇质体的特点及研究进展

醇质体作为一种新型脂质体,具有包封率高、变形性好、皮肤刺激性小、透皮效果佳、皮肤滞留量大、可以进行细胞内传递药物等优点,使其在经皮给药过程中更加有效.本文根据国内外文献,对醇质体的特点、透皮吸收性及在抗感染药、激素透皮给药、关节炎用药及大分子药物透皮递送等方面的应用进行综述,结果表明醇质体具有良好的应用前景和开发价值.     

含醇脂质体在透皮给药系统中的应用研究进展

目的 探讨含醇脂质体在透皮给药系统中的应用。方法 通过阐述脂质体在透皮给药系统中的特点、醇质体的制备、透皮吸收的实验及临床研究。了解含醇脂质体在透皮给药系统中的应用。结果 含醇脂质体应用于透皮给药系统具有许多优点,如醇质体能显著促进渗透。增加药物在皮肤中的滞留量。结论 含醇脂质体在透皮给药系统中的应用有巨大的发展潜力,有望成为一类新型的皮肤给药制剂。     

醇质体在经皮给药系统中的应用研究

目的:为醇质体在经皮给药系统中的应用提供参考。方法:以"醇质体""经皮给药""醇质体制备""Ethosomes""Transdermal drug delivery""Preparation of ethosomes"等为关键词,组合查询2000年1月-2017年5月在中国知网、PubMed、Elsevier、Springer等数据库中的相关文献,对影响醇质体经皮渗透的因素和醇质体的理化性质、制备方法、经皮吸收特点以及其毒性等方面进行综述。结果与结论:共检索到相关文献342篇,其中有效文献32篇。醇质体是由磷脂、高浓度醇、水构成的新型载药体系,其中醇能使醇质体流动性增强,磷脂能使醇质体更易穿过皮肤角质层;与脂质体比较,醇质体流动性更好、粒径更小、Zeta电位更低、稳定性更高、包封率更高。醇质体的制备方法简单,常用的方法有注入法、注入-超声结合法、薄膜分散法、pH梯度法。醇质体经皮渗透速率、药物经皮渗透累积量、药物在皮肤中滞留量较其他剂型显著提高;醇质体对皮肤无毒、无刺激。现已有盐酸苯海索、补骨脂素、熊果苷、芹菜素、氯诺昔康、睾酮、红霉素、利多卡因、栀子苷等药物的醇质体应用于经皮给药中。目前关于醇质体的研究很多还只是停留在简单的制备工艺、透皮吸收等实验阶段,而关于处方组成及比例对醇质体理化性质和透皮吸收效果的影响报道较少;关于醇质体皮肤滞留量的研究,多取自透皮吸收实验结束的时间点,缺乏动态的研究;有关醇质体的透皮吸收机制研究也不足。今后应从以上几方面着手,加强醇质体的基础研究。     

姜黄素醇质体体外透皮及其稳定性研究

目的：对姜黄素醇质体体外透皮及其稳定性进行考察方法：采用透皮扩散仪进行体外透皮实验,比较姜黄素醇质体、溶液、脂质体经小鼠离体皮肤的累积渗透量及皮肤滞留量;并将姜黄素醇质体4℃条件下冷藏,考察其稳定性。结果：姜黄素醇质体12h内单位面积皮肤的累计渗透量和皮肤滞留量是其溶液（含0．5％吐温-80）的2．71倍和2．81倍;但与其脂质体无显著差异。姜黄素醇质体4℃条件下冷藏1个月,其外观、包封率、粒径及多分散指数（PDI）变化较小。结论：醇质体作为透皮给药载体能促进姜黄素的透皮吸收,并能增加皮肤中的滞留量;姜黄素醇质体具有一定的稳定性。     

传递体透皮研究的最新进展

传递体(transfersomes)是一种自聚集泡囊,其主要组成成分为磷脂和表面活性剂(如胆酸钠、去氧胆酸钠等),亦称为柔性纳米脂质体.粒径多为几十个纳米,外观为胶体溶液.嵌人泡囊膜中的表面活性剂使泡囊具有高度的变形性.在外力的作用下,传递体与相同体积的纯水通过孔径数倍小于传递体直径的高分子膜的时间几乎相同,而普通脂质体通过高分子膜的时间明显延长.将传递体非封闭地涂抹于皮肤,可透过直径约为0.4 nm的皮肤角质层孔道,因此传递体有望成为大分子、小分子药物和水溶性、脂溶性药物的透皮载体.传递体一词由Cevc G等[1]首先提出,在随后的十几年中,Cevc G等在探索传递体的透皮机制并将数十种药物制备成传递体,经皮给药后产生了相应的药理效应.近年,国外每年均有传递体研究的文献报道,研究涉及的药物和内容也不断扩展.传递体中文一词在国内首次出现于丁平田[2]所写的一篇有关传递体研究综述.近年来,国内也不断出现有关传递体的研究报道.本文将对传递体的特性、体外透皮研究、体内透皮研究、稳定性、药效学研究及展望等方面作一介绍.     

离子导入透皮给药的研究

许多药物透皮给药后的渗透速率达不到治疗要求,所以寻找促进药物渗透皮肤的方法是开发经皮给药系统的关键之一。常用的方法是选择合适的皮肤渗透促进剂和合成具有理想透皮性能的前体药物,但前者可能引起皮肤生理和生化改变,后者常需较复杂的研究工作。近来一个物理学方法——离子导入法(Iontophoresis)已被引入透皮给药研究中,它可以促进一些药物特别是离子型药物及多肽类大分子的透皮吸收。离子导入是指在直流电的作用下,离子型药物从溶液中通过皮肤渗透进入组织,阳离子在阳极进入皮肤,阴离子在阴极进入皮     

醇质体的研究进展

目的:了解作为经皮给药载体的醇质体的研究进展。方法:根据文献,综述了醇质体在选用药物的条件、组成、制备方法、理化特性及体外透皮吸收等方面的信息。结果与结论:有效治疗剂量小、透皮速率足够大的药物可制备成醇质体;醇质体一般组成为低分子量的醇、磷脂和水;制备方法包括注入法、注入-超声结合法、薄膜分散法和pH梯度法;其形态多为球形或近球形的多室囊泡,结构较稳定,Zeta电位一般为负值,包封效果较优;渗透速率较相应的脂质体和水醇溶液快,透皮量和皮肤中累积量也相对较高。由于其无毒性及皮肤刺激性,是皮肤透皮给药较理想的载体。     

透皮促进剂对萘普生的促透效果研究

目的研究透皮促进剂月桂氮酮、油酸、月桂醇与1,2-丙二醇单独使用或混合使用对萘普生经皮渗透的促透效果。方法采用Valia-Chien双室渗透池,以10%聚乙二醇400生理盐水为接收介质,经大鼠腹部离体皮肤渗透,高效液相色谱法测定接受液中药物含量,计算药物累积透皮量和稳态透皮速率。结果 5%月桂氮酮+20%1,2-丙二醇达最大促透效果。结论脂溶性促进剂月桂氮酮、油酸,联合1,2-丙二醇使用对萘普生促透效果显著。     

传递体作为双氯芬酸钠经皮渗透载体的体外研究

目的传递体作为双氯芬酸钠经皮渗透载体的体外研究.方法采用改良Franz扩散池体外经皮渗透实验技术,对双氯芬酸钠传递体、普通脂质体及其凝胶剂的经皮渗透作用进行了比较.结果24 h后双氯芬酸钠传递体、普通脂质体及其凝胶剂的累积透皮量分别为598.16μg·cm-2,209.15μg·cm-2,391.33μg·cm-2.皮肤内滞留量Q滞分别为191.54μg·cm-2,419.28μg·cm-2,8.77μg·cm-2.结论以传递体作为双氯芬酸钠的载体可以促进其经皮渗透,且皮内的滞留药物还表现出一定的贮库效应.而普通脂质体不能很好地促进药物透过皮肤,但利于药物在皮内的大量滞留.     

纳洛酮醇质体凝胶复合物的经皮渗透研究

目的设计纳洛酮醇质体凝胶复合物,考察不同浓度的羟丙甲纤维素(HPMC)以及纳洛酮醇质体凝胶复合物与化学促渗剂联合应用对体外透皮速率的影响。方法采用注入法制备醇质体,HPMC制备凝胶,以SD雄性大鼠皮肤为媒介,改良Franz单室扩散池为体外模型,用HPLC法测定透过皮肤的纳洛酮含量。求算稳态透皮速率和皮肤中的滞留量。结果纳洛酮为2mg·mL-1时,HPMC作为纳洛酮醇质体基质时经皮渗透速率为1%HPMC>3%HPMC>5%HPMC>醇质体>10%HPMC。二甲基亚砜的促渗效果最好,且随二甲基亚砜浓度增加,稳态渗透速率增加。结论适当浓度的HPMC作为纳洛酮醇质体的基质时,能提高纳洛酮醇的透皮速率,增加药物在皮肤中的滞留量,醇质体凝胶复合物有望开发为纳洛酮经皮给药的新剂型。     

Percutaneous penetration enhancers: an overview

Transdermal drug delivery is the controlled release of drugs through the skin to obtain therapeutic levels systematically. Several technological advances have been made in the recent decades to enhance percutaneous drug penetration. This overview focuses on the physical, biochemical, and chemical means of penetration enhancement, as well as the classification and mechanisms of chemical penetration enhancers, their application in transdermal drug delivery, and trends and development in penetration enhancement.     

微针技术在经皮给药中的应用

微针是经皮给药的物理促渗方法之一,有着很好的市场前景。本文介绍微针的透皮促渗机制、促进药物经皮渗透的因素、复合技术以及微针在大分子经皮促渗中的应用。     

An investigation into the transdermal delivery of nifedipine

A systematic attempt to develop a transdermal delivery system for nifedipine is presented. Measured physicochemical properties influencing percutaneous absorption such as solubility and partition coefficient confirmed the drug's potention for such a formulation approach. However, studies involving permeation through hairless mouse skin from a range of hydrophilic and hydrophobic donor vehicles indicated inadequate penetration. Attempts to increase the drug flux through the animal skin or a range of artificial membranes alone or in parallel by use of the penetration enhancers sodium lauryl sulphate 1% and propylene glycol 20% in a sodium carboxymethylcellulose 3% gel base failed to raise the drug flux to an acceptable level. Likewise increase in the drug thermodynamic gradient across the skin by use of mixed solvents or supersaturated drug solutions was ineffective if an aqueous receiving phase was used. Collectively the results suggest that the development of a transdermal delivery system for the chemically unmodified drug in humans is unlikely to be successful.     

Prodrugs for transdermal drug delivery – trends and challenges

Prodrugs continue to attract significant interest in the transdermal drug delivery field. These moieties can confer favorable physicochemical properties on transdermal drug delivery candidates. Alkyl chain lengthening, pegylation are some of the strategies used for prodrug synthesis. It is usually important to optimize partition coefficient, water and oil solubilities of drugs. In this review, progress made in the field of prodrugs for percutaneous penetration is highlighted and the challenges discussed.     

Physicochemical, physiological, and mathematical considerations in optimizing percutaneous absorption of drugs

The percutaneous absorption or transdermal permeation of drugs has gained considerable prominence in recent years through the development of transdermal systemic delivery systems and the related interest in the design and use of topical products. The present review discusses the phenomenon of percutaneous absorption in drug delivery and its importance in regard to the anatomy of skin, its physiological function, and biomechanical properties, as well as the physicochemical properties of the skin and the drug. The mathematical relationships and models used to describe the phenomenon of percutaneous absorption are also reported. The importance of these factors in optimizing percutaneous absorption or transdermal permeation of drugs for local or systemic effect is also discussed.     

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。     

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.     

微针的特点及其在黄褐斑治疗中的应用研究分析

黄褐斑是一种后天获得性色素沉着性疾病，困扰患者的工作和生活。外用经皮给药的主要挑战是药物透过角质层屏障的阻碍。微针作为物理促渗方法和新的递药系统，能够穿透角质层形成特定的药物输送通道，促进了药物的渗透，提高了药物的生物利用度。本文主要总结了微针的特点，并以黄褐斑为切入点，分析微针近年来在黄褐斑领域的应用研究，为后续黄褐斑微针产品的开发提供一定的参考。     

New tools and approaches for predicting skin permeability

This article reviews some new mathematical models and techniques used to predict and understand percutaneous penetration and transdermal delivery. These models are also useful for various enhancement strategies that can be used in dermal-penetration and formulation development studies. If appropriate, biophysical techniques can be combined with these new mathematical models and statistical analyses and it will be possible to understand the factors affecting penetration of molecules through skin. These factors, or parameters, can then be used to control the penetration rate when effective transdermal delivery or therapy is required or targeted.     

奥沙普秦凝胶剂体外透皮实验条件及促渗剂的选择

目的 :考察载药量、介质组成、促渗剂月桂醇(LA)和氮酮(AZ)对奥沙普秦(OXP)凝胶剂体外透皮作用的影响。方法 :采用改良Franz双室渗透装置 ,以离体小鼠皮肤为透皮屏障 ,进行体外渗透试验。结果 :在有效透过面积5 77cm2条件下 ,载药量大于1 2g ,接收液乙醇∶生理盐水=7∶3(v∶v)时 ,实验结果稳定 ,重现性好 ;月桂醇促渗作用强于氮酮 ,混合促渗剂3 %AZ +10 %LA效果最佳。结论 :通过对OXP凝胶最佳透皮实验条件和促渗剂的选择 ,为研究OXP透皮给药提供了参考依据 ,同时对凝胶剂体外透皮试验的标准化进行了初步探讨。