超声波技术在透皮药物传递系统中的应用

目的介绍超声波促进药物透皮吸收的物理方法的研究成果和进展。方法通过查阅国内外文献进行归纳和综述。结果与结论超声经皮给药促渗技术能够提供数倍于常规给药方法的持续稳定的渗透率,是一种极具潜力的给药方式,而且与其他方法联合应用的促渗效果更加显著。     

多肽透皮给药研究进展

针对近年来多种多肽类药物的透皮给药系统进行综述。通过查阅国内外多种相关期刊文献。将多肽类药物透皮给药方法分为化学促渗剂、多种物理促渗技术,以及透皮肽、微针技术并对其进行论述。反向离子导入技术应用前景广阔,微针给药系统研究逐步深入,出现了胰岛素智能化微针给药系统,透皮肽的研究发展迅速,相信未来多种蛋白质及多肽的透皮给药方式将应用于临床,极大地促进医疗事业的发展。     

经皮离子导入影响因素研究进展

经皮离子导入是指在外加电场作用下 ,促进药物离子通过皮肤转运的一种经皮给药物理促渗方法。离子导入受到越来越多的关注 ,科学工作者不断探索影响离子导入的因素 ,为离子导入透皮给药技术的临床应用提供依据。1　药物的物理化学性质1.1　药物所带电荷理论上认为化合物离子导入给药速率同其所带的电荷成正比。近来有人研究了人胰岛素同系物对无毛小鼠离子导入渗透速率的影响[1] 。采用不带电荷的人胰岛素阴极导入 ,仅仅发现有很低的速率通过皮肤。而当使用 2价负电荷的人胰岛素 ,其渗透速率提高了 5 0～ 10 0倍。采用带 3价负电荷的人胰岛…     

非甾体抗炎药透皮给药的研究进展

目的:介绍非甾体抗炎药经皮给药的进展。方法:就常见非甾体抗炎药的透皮剂型、促渗方法和透皮模型进行综述。结果与结论:研究非甾体抗炎药经皮给药对此类药物的透皮制剂开发有重要意义。     

乙醇脂质体透皮作用的研究与发展

目的：介绍乙醇脂质体透皮作用的研究与发展。方法：综合分析乙醇脂质体的组成及一般特性、制备及乙醇脂质体载药系统透皮给药的药剂学促透机制、最新的基础实验和研究进展。结果：作为各种药物的载体，乙醇脂质体具有其良好的药物包裹率和显著的促进药物透皮吸收特性。结论：乙醇脂质体新剂型透皮给药具有广阔的应用前景。     

透皮促进剂在透皮吸收制剂中的应用

透皮给药是一个新兴的领域 ,具有许多优点而受到药学工作者的重视。其理论基础为给药后药物能迅速穿透皮肤 ,被吸收进入血液循环而产生疗效。因此 ,研究经皮给药制剂首先必须解决药物对皮肤的穿透性和透皮速率。安全、有效、作用强的透皮促进剂的开发应用 ,已成为药学工作者的研究重点。1　新型促渗剂①目前使用最多的是氮酮 (Ａｚｏｎｅ) ,对亲水性或疏水性药物都能显著增强透皮速率。Ｍｉｃｈｎｉａｋ等[1] 合成了 2 吡咯烷酮 1 醋酸及其各种酯类、Ｎ 环庚基酰胺类同系物和Ａｚｏｎｅ的 11个同系物 ,以考察其对氢化可的松的促渗作用。结…     

纳米制剂在透皮药物递送系统中的应用研究进展

透皮药物递送系统作为一种非侵入式给药途径，与传统给药方式相比具有顺应性高、无首过效应等优势。纳米技术的应用使得透皮药物递送系统的药物选择范围进一步扩大，并提高了药物的治疗效果，形成了一种极具价值、令人期待的新型给药方式。目前常用于透皮药物递送系统的纳米制剂包括纳米乳、脂质纳米囊泡、脂质纳米粒、聚合物纳米粒、纳米晶体、溶致液晶纳米粒等。介绍了皮肤屏障和透皮递送的常用促渗方法，综述了各类应用于透皮药物递送系统的纳米制剂及其与物理促渗方法联合应用的研究进展，以期为纳米制剂在透皮递送方面的深入研究提供参考。     

促进药物透皮吸收的方法及应用前景

介绍透皮给药制剂的研究进展及促进药物透皮渗透的方法。通过促进药物的透皮吸收，可减少药物的某些首过作用和增加用药顺应性。促进药物透皮渗透的方法主要有添加促透剂、物理方法、制成脂质体及环糊精等。透皮吸收制剂经皮给药，可达到全身治疗的目的，服药顺应性好，患者特别是儿童乐于接受。     

电致孔技术在透皮给药中的应用

电致孔可显著提高药物的经皮吸收,有望用于多肽和蛋白质类生物大分子药物的透皮给药.本文对电致孔法的透皮促渗机制、影响因素以及安全性进行了讨论,并介绍了有关实验装置及其在透皮给药中的应用.     

离子导入经皮给药系统

综述了离子导入技术的基本组成、促渗机制、影响因素及应用前景。离子导入技术可有效提高药物的经皮渗透性，该技术扩大了经皮给药系统的研究范围，其对多肽和蛋白质等大分子药物的透皮促渗作用日益受到关注。     

Fluorescein permeability and electrical resistance of human skin during low frequency ultrasound application

Transdermal drug delivery offers an alternative to injections and oral medication but is limited by the low skin permeability of most drugs. The use of low-frequency ultrasound over long periods of time, typically over an hour, has been shown to enhance skin permeability, a phenomenon referred to as sonophoresis. In this study, we investigated the effects of short time sonication of human skin at 20 kHz and at variable intensities and duty cycles on the dynamics of fluorescein transport across the skin (permeability) as well as the changes in the skin's structural integrity (electrical resistance). We found that a short application of ultrasound enhanced the transport of fluorescein across human skin by a factor in the range of 2-9 for full thickness skin samples and by a factor in the range of 2-28 000 for heat-stripped stratum corneum samples (however, samples with very high (10(3)) enhancement were likely to have been damaged by ultrasound). The electrical resistance of the skin decreased by an average of 20% for full thickness samples and 58% for stratum corneum samples. Increasing the duty cycle from 10 to 60% caused a significant increase in permeability enhancement from 2.3 to 9.1, and an increase in intensity from 8 to 23 mW cm(-2) induced a significant increase in permeability enhancement from 2 to 7.4, indicating a clear dependence of the permeability on both duty cycle and intensity. The increase in solute flux upon ultrasound exposure was immediate, demonstrating for the first time the fast response dynamics of sonophoretic enhancement. In addition, a quantitative analysis of the thermal and convective dispersion effects associated with ultrasound application showed that each contributes significantly to the overall permeability enhancement observed.     

Transdermal delivery of tea catechins by electrically assisted methods

Tea polyphenols, including (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin-3-gallate (EGCG), have been shown to possess potent antioxidant and chemopreventive activities. The aim of this study was to assess the effects of electroporation, iontophoresis, and their combination on the transdermal delivery of tea catechins across porcine skin. The permeation characteristics were investigated using various analogues of catechins, pH values, and modes of electroporation and iontophoresis. The mechanisms by which these catechins were transported via the skin were elucidated by examining the electric conductivity, transepidermal water loss (TEWL), and fusion of stratum corneum lipid liposomes (SCLL). The isomers, (+)-catechin and (-)-epicatechin, showed different behaviors of skin permeation and local skin deposition with the electrically assisted methods. The results suggest evidence of selective skin absorption of (-)-epicatechin over (+)-catechin. A synergistic effect was detected for (+)-catechin but not for (-)-epicatechin after application of electroporation followed by iontophoresis. The presence of a gallic acid ester in the structure of EGCG significantly increased the skin uptake of catechins. However, a negligible amount of or no EGCG molecules permeated across the skin. The mechanisms involved in the enhancement of electroporation may be the skin reservoir effect and an increase in skin permeability. The TEWL profiles suggest that in addition to the force of electrorepulsion, the skin hydration effect and structural alterations may also have contributed to the enhancement by iontophoresis. Electroporation did not influence the skin barrier function, although the skin permeability increased according to the SCLL fusion study.     

Effect of abrasion induced by a rotating brush on the skin permeation of solutes with varying physicochemical properties.

A transient reduction in the barrier nature of the skin can be a pre-requisite for successful (trans)dermal delivery of some drugs. The aim of this present study was to investigate and effect of a dermal abrading "rotating brush" device on percutaneous absorption and skin integrity. In vitro experiments were conducted using excised human epidermal membrane. The effect of device parameters (bristle type, treatment duration and applied pressure) on skin permeability of model solutes (methyl paraben, butyl paraben, caffeine, acyclovir and angiotensin II) with varying physicochemical properties was examined and compared to established methods of skin penetration enhancement (positive controls). The device parameter which was found to have the most marked effect on permeability of the compounds was bristle type. Profound changes (2- to 100-fold increase) were observed in the epidermal permeability of the hydrophilic penetrants (caffeine, acyclovir and angiotensin II), when the brush device was employed compared to positive controls (ethanol enhancement, delipidisation, iontophoresis and tape-stripping). Findings from this present study support the effectiveness of a rotating brush applied to the skin in enhancing epidermal permeability. Further optimization of operational parameters is required to exploit this simple and effective delivery device.     

Evaluation of the porosity, the tortuosity, and the hindrance factor for the transdermal delivery of hydrophilic permeants in the context of the aqueous pore pathway hypothesis using dual-radiolabeled permeability experiments

The aqueous pore pathway hypothesis has been modified to include both transient and steady-state domains of diffusive transport to evaluate the porosity, the tortuosity, and the hindrance factor of the skin aqueous pore channels from an individual dual-radiolabeled permeability experiment. Using these theoretical and experimental methods, the porosity (epsilon), the tortuosity (tau), and the hindrance factor (H) of the skin aqueous pore channels were evaluated as a function of: (i) the radius of the selected model hydrophilic permeants (urea, mannitol, raffinose, and inulin), and (ii) the extent of skin perturbation present in untreated skin, skin pretreated at a low dose, and a high dose, with a simultaneous application of 20 kHz ultrasound and the surfactant sodium lauryl sulfate (SLS), and the dermis. The results of this investigation revealed that the tortuosity decreased, and only the hindrance factor for inulin was significantly less than 1, over the range of permeant radii examined. Furthermore, only the porosity increased over the range of skin perturbation examined (over 100-fold), suggesting that a surface-related phenomenon is primarily responsible for the observed enhancement in the transdermal permeability of hydrophilic permeants induced by the simultaneous application of ultrasound and SLS.     

Effect of low frequency ultrasound on the in vitro percutaneous absorption of clobetasol 17-propionate.

The effect of low frequency ultrasound (20 kHz) on the permeation of clobetasol 17-propionate (CP) through skin (sonophoresis) was studied. The ultrasound was applied at either continuous or discontinuous modes and at different intensities. The results showed that low frequency ultrasound significantly enhanced the permeability of CP across hairless mouse skin in vitro. Delivering the same amount of ultrasonic energy in different modes of application markedly influenced the flux and skin residual of CP. The on/off discontinuous ultrasound had greater enhancement on CP permeation than the continuous ultrasound. The results of skin histopathology and permeation experiment using various membranes demonstrate that both disordering of stratum corneum and convective flow resulted from the cavitation effect were responsible for sonophoretic enhancement of CP. The permeation of CP through hair follicles and sweat ducts was susceptible to the application of ultrasound.     

3种溶剂对来氟米特离体皮肤渗透的影响

目的：研究溶剂对来氟米特离体皮肤渗透的影响,方法：采用改良Franz扩散池,以离体小鼠皮肤为渗透屏障,渗透速率为指标,HPLC法测定来氟米特浓度,结果：乙醇对来氟米特皮肤渗透有一定的促进作用,丙二醇和低浓度1,3－二甲基2－咪唑啉酮（DMI）对来氟米特的皮肤渗透影响不大,结论：3种溶剂都可用于来氟米特皮肤局部用制剂。     

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。     

Topical DNA vaccination with DNA/Lipid based complex

Topical DNA vaccines have been shown to elicit both broad humoral and cellular immune response in vivo. The skin is an attractive site for the delivery DNA antigens for DNA vaccination. However, due to skin's barrier properties, the penetration of DNA and the applications of topical vaccination are limited. To improve permeability of stratum corneum and the potency of topical DNA vaccines, efficient delivery systems are needed. Topical vaccination has been achieved using topical application of naked DNA with or without tape stripping and DNA/lipid based complex such as liposomes, niosomes, Transfersomes, or microemulsion. All methods resulted in significant enhancement in humoral and cellular immune response over naked DNA alone. To develop more cost-effective and needle free vaccines, skin targeted immunizations are required. This overview focuses on the comparison of the potency of topical DNA vaccine between naked DNA and DNA-lipid based complex.     

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.     

Enhancement of transdermal absorption by switching iontophoresis

The enhancing effect of switching iontophoresis on transdermal absorption of phthalic acid (PA), benzoic acid (BA), salicylic acid (SA), p-phenylenediamine (PD), aniline (AN) and verapamil (VR) and its mechanism were examined. An electric current with pulsed waveform (4 kHz, 50% duty) was passed through the skin for 2 h at 10 V. Iontophoretic application was carried out with switching at intervals of 5, 10 and 20 min, or without switching. Each drug solution was injected into the donor side of the cell, and phosphate buffer (pH 7.4) was injected into the receiver side. Transport of PA, BA and VR was affected by switching the polarity of electrodes but no effect was observed on that of SA, PD and AN. Cumulative amount permeated and apparent permeability coefficients were apparently high at switching intervals with a short period. The partition coefficient suggested that there was no interrelation between the affinity for skin and the permeability of each drug. The resistance values of PA and glucose were low at intervals of 5 min suggesting the participation of enhanced hydration of the skin. These results suggested that enhancement of skin hydration plays an important role in the enhancing effect of switching iontophoresis on skin permeation.