化学促渗剂在经皮给药系统中的应用进展

皮肤作为有效的机体保护屏障,既可使机体不受外界物质的侵入,又能防止皮肤内生理物质的流失。但对于经皮给药系统(transdermal drug delivery systems,TDDS)来说,为使治疗药物尽可能多地在给药部位吸收,常规策略是使用可以和皮肤组织相互作用的物质———促渗剂(chemical pen-e     

经皮给药系统促渗方法研究的新进展

促渗方法的发展对于经皮给药的研究意义重大。笔者从化学促渗技术，包括化学促渗剂、前体药物、传递体、含醇脂质体、非离子表面活性剂脂质体和微乳；以及物理促渗技术，包括离子导入、电致孔、超声波促渗、微针、照相波、热致孔和磁场导入等诸多方面综述了近年来经皮给药促渗方法研究的新进展。     

壳聚糖及其衍生物在眼部给药系统中的研究进展

壳聚糖是一种阳离子型天然黏多糖,具有无毒、生物黏附性、生物相容性、促渗透性、生物可降解性和假塑性等优点,己被广泛应用于眼部给药系统中.本文综述了壳聚糖有关性质及其在眼部给药系统中的研究状况和局限性,旨在为壳聚糖在眼部给药系统中的进一步应用提供参考.     

国外经皮给药系统的研究进展

经皮给药系统(Transdermal drug delivery system,TDDS)是一种研究得较为广泛的给药系统,其给药剂型一般为贴片(Patch).近年来,随着对TDDS机制的不断深入研究及各种促渗技术的相继开发,其正突破传统向一类重要的非口服制剂发展.为全面了解其发展现状及趋势,笔者查阅相关文献,就国外TDDS的进展做一简要介绍.     

壳聚糖及其衍生物在智能给药系统中的应用

本文从单重敏感性智能给药系统、多重敏感性智能给药系统及生物传感器着手,主要介绍了壳聚糖及其衍生物在智能给药系统中的研究进展,并展望了其在智能给药系统中的应用前景。     

壳聚糖及其衍生物在肽类口服给药系统的应用

壳聚糖作为药用辅料在药剂领域中的地位愈加显著,将聚β１→４Ｄ－葡萄糖胺的２位氨基进行修饰,可获得具不同功能的壳聚糖类衍生物,对于口服氨基酸第系统来说,最主要的是克服胃肠道的吸收屏障及酶屏障,未经化学修饰的壳聚糖对肽类药物具有一定的促渗作用。将抑制剂固定于聚合物结构内则对肠肽酶对肽类的降解产生保护作用,胰丝氨酸蛋白酶的降解作用可被竞争性抑制剂如Ｂｏｗｍａｎ－Ｂｉｒｋ抑制剂所抑制,而金属肽酶的降解作用则可被壳聚糖－ＥＤＴＡ复合物等性质较复杂的壳聚糖衍生物所抑制,而且,由于壳聚糖及其大部分衍生物都具有粘膜粘附特性,多肽药物的吸收前代谢也大大降低,综合以上因素,壳聚糖及其衍生物可显著提高某些肽类药物如胰岛素、降钙素及布舍瑞林口服给药的生物利用度,是肽类口服给药系统中的一类重要辅料。     

微乳在经皮给药系统中的应用

微乳经皮给药是目前国内外药学工作者研究的重点,也是目前药物制剂研发热点之一。本文主要从微乳的组成、促渗机制、微乳在经皮给药中的应用3个方面进行了综述。微乳经皮给药具有很好的应用前景。     

聚合物胶束在经皮给药系统中的应用

摘 要 目的：综述聚合物胶束作为药物载体在经皮传递系统中的应用进展。方法: 根据国内外发表的最新文献,对聚合物胶束的制备方法、促进皮肤渗透的机制、释药过程及其在经皮给药系统中的应用进行分析与讨论。结果: 聚合物胶束具有增加难溶性药物的溶解度,促进药物的经皮吸收等作用,作为药物载体在经皮传递系统的应用越来越广泛。结论:聚合物胶束可作为药物载体被广泛用于经皮给药系统的研究中,具有较好的发展前景。     

经皮给药促透方法的研究进展

目的由于皮肤的屏障作用,经皮给药系统的应用受到限制,促透方法的研究成为焦点。许多方法可用于促进药物的经皮吸收。本文主要从化学法、物理法、药剂学法、生物法及促透方法的综合应用等方面阐述了近年来国内外在经皮给药促透方法的研究上所取得的进展。     

经皮给药系统的研究进展

经皮给药系统是目前国内外药学工作者研究的重点,也是目前国内新药研究的主要方向之一.主要从经皮给药系统的特点及优势、经皮给药制荆及促渗方法的研究和进展3个方面进行了综述,并对经皮给药系统的发展前景进行了展望,说明经皮给药系统具有广阔的发展前景,并有利于实现我国的中药现代化.     

Assessment of chitosan derivatives as buccal and vaginal penetration enhancers.

The aim of the present work was to evaluate the mucoadhesive and penetration enhancement properties via the buccal and vaginal mucosae of four different chitosan derivatives: 5-methyl-pyrrolidinone chitosan (MPC), two low molecular weight chitosans (DC1 and DC2) and a partially reacetylated chitosan (RC). Chitosan HCl was used as a reference. Polymer solutions (4% w/w) were prepared in media simulating the buccal (pH 6.4 buffer or water) and the vaginal (pH 5.0 buffer) environments and subjected to rheological characterization. Acyclovir was added to the polymer solutions at 5% (w/w) concentration. The mucoadhesive properties of the polymer solutions were measured using excised porcine cheek or vaginal mucosa and mucin dispersions to simulate the buccal or vaginal environments, respectively. Drug permeation and penetration tests were carried out using porcine cheek and vaginal mucosae as model membranes. Acyclovir aqueous suspensions prepared in pH 6.4 and 5.0 buffers were used as blanks. Drug release measurements were also carried out in the same conditions employed for the permeation and penetration tests. Methyl-pyrrolidinone chitosan shows the best mucoadhesive and penetration enhancement properties in both buccal and vaginal environments. The capability to enhance the permeation/penetration of acyclovir was decreased by partial depolymerization of chitosan and disappeared after partial reacetylation.     

Preparation of alkyl-substituted pyrrolidone derivatives and their evaluation as transdermal penetration enhancers.

The preparation of novel transdermal penetration enhancers derived from 2-pyrrolidone were carried out, and the enhancing activities of drug permeation through the skin were evaluated by means of in vitro experiment. All the enhancers contain a short alkyl group, such as methyl, ethyl, propyl or butyl group, at 1-position and a dodecyl group at 3-position of 2-pyrrolidone ring. The enhancing activities were considerably influenced by the length of the short alkyl group at 1-position. 1-Propyl and 1-butyl-3-dodecyl-2-pyrrolidone showed the effective enhancement of penetration of indomethacin through the skin in 60 wt% ethanolic aqueous solution. Moreover, the similar enhancing activities of these compounds were also observed even in ethanolic vehicle.     

Biomaterials as novel penetration enhancers for transdermal and dermal drug delivery systems

Abstract

The highly organized structure of the stratum corneum provides an effective barrier to the drug delivery into or across the skin. To overcome this barrier function, penetration enhancers are always used in the transdermal and dermal drug delivery systems. However, the conventional chemical enhancers are often limited by their inability to delivery large and hydrophilic molecules, and few to date have been routinely incorporated into the transdermal formulations due to their incompatibility and local irritation issues. Therefore, there has been a search for the compounds that exhibit broad enhancing activity for more drugs without producing much irritation. More recently, the use of biomaterials has emerged as a novel method to increase the skin permeability. In this paper, we present an overview of the investigations on the feasibility and application of biomaterials as penetration enhancers for transdermal or dermal drug delivery systems.     

Preparations of phosphonate, phosphoramidate and phosphate derivatives and their evaluation as transdermal penetration enhancers.

Phosphonate, phosphoramidate and phosphate derivatives containing long alkyl groups were prepared, and their activities enhancing drug penetration through the skin were evaluated by means of in vitro experiments. The effect of chemical structure of these compounds on enhancing activity was investigated. Among the phosphonate and phosphoramidate derivatives, compounds having a hexadecyl group showed the most effective enhancement of transdermal penetration of indomethacin. For the phosphate derivatives, the enhancing activities were almost equal in the compounds containing dodecyl, tetradecyl and hexadecyl group. All the compounds having an octyl group were not effective in penetration enhancement. Diethyl hexadecylphosphonate and diethyl hexadecylphosphoramidate brought about the highest enhancing activities among these compounds, and the permeability coefficient of indomethacin was about 10-fold as much as that without enhancer. The relationship between the enhancing activities and the lipophilicities of these compounds was discussed.     

透皮吸收促进剂在经皮给药系统中的质控和评价方法

透皮吸收制剂是国际上第三代药物制剂的研究重点领域。透皮吸收促进剂在处方中的合理应用和质量控制及其评价方法日益重要。通过对透皮促进机理、协同作用等的探讨,介绍透皮吸收促进剂的选用原则,并对透皮给药制剂和局部用药局部起效的皮肤外用制剂处方中使用的要求加以讨论,介绍了现有的评价方法和基本的技术要求。     

非洛地平-美托洛尔复方贴剂的透皮吸收促进剂优化

目的：优化复合透皮吸收促进剂，制备非洛地平-美托洛尔复方贴剂，并对其外观、物理特性、体外药物释放和经皮渗透性能进行综合评价。方法：以药物体外释放速率和稳态透皮速率为指标，通过正交设计试验考察桉叶油醇、月桂氮[艹卓]酮和丙二醇体系对贴剂质量的影响，优选最佳复合透皮吸收促进剂构成。结果：优选的透皮吸收促进剂最佳含量分别为桉叶油醇5％、月桂氮[艹卓]酮3％和丙二醇12%，以该促透体系制备的贴剂药物体外释放速率和稳态透皮速率高，外观和理化特性较佳，物理黏性适宜，各指标均达到预期设计要求。结论：桉叶油醇-月桂氮[艹卓]酮-丙二醇（5：3：12）复合体系对非洛地平和关托洛尔的协同促透作用显著，且稳定可靠，是非洛地平关托洛尔复方贴剂的优良透皮吸收促进剂。     

作为基因输送载体的壳聚糖衍生物研究进展

壳聚糖作为基因载体,目前存在的主要问题是还不能达到足够高的表达效率。其中主要原因是壳聚糖在pH 7.4的生理环境下溶解度较差,壳聚糖与DNA形成的复合物在生理环境下的稳定性较差,缺乏细胞靶向性。本文综述了作为基因输送载体的壳聚糖衍生物研究进展,为进一步研究和开发壳聚糖衍生物提供依据和参考。     

Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery

Transdermal drug delivery (TDD) is the administration of therapeutic agents through intact skin for systemic effect. TDD offers several advantages over the conventional dosage forms such as tablets, capsules and injections. Currently there are about eight drugs marketed as transdermal patches. Examples of such products include nitroglycerin (angina pectoris), clonidine (hypertension), scopolamine (motion sickness), nicotine (smoking cessation), fentanil (pain) and estradiol (estrogen deficiency). Since skin is an excellent barrier for drug transport, only potent drugs with appropriate physicochemical properties (low molecular weight, adequate solubility in aqueous and non-aqueous solvents, etc) are suitable candidates for transdermal delivery. Penetration enhancement technology is a challenging development that would increase significantly the number of drugs available for transdermal administration. The permeation of drugs through skin can be enhanced by physical methods such as iontophoresis (application of low level electric current) and phonophoresis (use of ultra sound energy) and by chemical penetration enhancers (CPE). In this review, we have discussed about the CPE which have been investigated for TDD. CPE are compounds that enhance the permeation of drugs across the skin. The CPE increase skin permeability by reversibly altering the physicochemical nature of the stratum corneum, the outer most layer of skin, to reduce its diffusional resistance. These compounds increase skin permeability also by increasing the partition coefficient of the drug into the skin and by increasing the thermodynamic activity of the drug in the vehicle. This review compiles the various CPE used for the enhancement of TDD, the mechanism of action of different chemical enhancers and the structure-activity relationship of selected and extensively studied enhancers such as fatty acids, fatty alcohols and terpenes. Based on the chemical structure of penetration enhancers (such as chain length, polarity, level of unsaturation and presence of some special groups such as ketones), the interaction between the stratum corneum and penetration enhancers may vary which will result in significant differences in penetration enhancement. Our review also discusses the various factors to be considered in the selection of an appropriate penetration enhancer for the development of transdermal delivery systems.