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。     

Iontophoretic drug delivery using the IOMED Phoresor® system

Iontophoresis, or electromotive drug administration, is a process that enhances the delivery of drugs through a biological membrane via the application of low-intensity electrical current. This technology offers several advantages over oral and injection drug delivery. Key advantages of iontophoretic drug delivery include the avoidance of pain and potential for infection associated with needle injection, the ability to control the rate of drug delivery, the ability to programme the drug-delivery profile and the minimisation of local tissue trauma. Research using iontophoresis has shown delivery of a number of drug classes. By controlling the applied electric current one can tailor a dosage regimen with a drug delivery profile specific for an indication and the needs of the patient. Advances in iontophoretic electrode design, microelectronics and methods to optimise iontophoretic drug delivery have improved the ability to safely deliver both older, off-patent drugs, as well as new chemical entities being developed to treat a variety of diseases. In addition to transdermal applications, current research indicates that iontophoresis may prove to be a viable noninvasive drug delivery method for treating conditions that affect the back of the eye.     

物理方法促进胰岛素经皮吸收的实验研究进展

目的胰岛素经皮吸收制剂是一种理想的胰岛素给药方式,但由于皮肤角质层的阻力、胰岛素分子在皮肤中的累积等因素限制了胰岛素的经皮给药。方法本文介绍了微针、电致孔、超声导入、离子导入等物理方法促进胰岛素经皮吸收实验研究进展。结果研究安全、有效、经济、方便的胰岛素透皮吸收物理促渗技术。结论随着对上述新技术、新方法实验研究的深入,物理促渗技术必将为胰岛素透皮吸收制剂的发展开辟更广阔的前景     

Nanoemulsions as potential vehicles for transdermal and dermal delivery of hydrophobic compounds: an overview

Introduction: In recent years, nanoemulsions have been investigated as potential drug delivery vehicles for transdermal and dermal delivery of many compounds especially hydrophobic compounds in order to avoid clinical adverse effects associated with oral delivery of the same compounds. Droplet size and surface properties of nanoemulsions play an important role in the biological behavior of the formulation.

Areas covered: In this review, current literature of transdermal and dermal delivery of hydrophobic compounds both in vitro as well as in vivo has been summarized and analyzed.

Expert opinion: Nanoemulsions have been formulated using a variety of pharmaceutically acceptable excipients. In many cases of dermal and transdermal nanoemulsions, the skin irritation or skin toxicity issues on human beings have not been considered which needs to be evaluated properly. In the last decade, much attention has been made in exploring new types of nanoemulsion-based drug delivery system for dermal and transdermal delivery of many hydrophobic compounds. This area of research would be very advantageous for formulation scientists in order to develop some nanoemulsion-based formulations for their commercial exploitation and clinical applications.     

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。     

Novel reverse electrodialysis-driven iontophoretic system for topical and transdermal delivery of poorly permeable therapeutic agents

Topical and transdermal drug delivery has great potential in non-invasive and non-oral administration of poorly bioavailable therapeutic agents. However, due to the barrier function of the stratum corneum, the drugs that can be clinically feasible candidates for topical and transdermal delivery have been limited to small-sized lipophilic molecules. Previously, we fabricated a novel iontophoretic system using reverse electrodialysis (RED) technology (RED system). However, no study has demonstrated its utility in topical and/or transdermal delivery of poorly permeable therapeutic agents. In this study, we report the topical delivery of fluorescein isothiocyanate (FITC)–hyaluronic acid (FITC–HA) and vitamin C and the transdermal delivery of lopinavir using our newly developed RED system in the in vitro hairless mouse skin and in vivo Sprague–Dawley rat models. The RED system significantly enhanced the efficiency of topical HA and vitamin C and transdermal lopinavir delivery. Moreover, the efficiency and safety of transdermal delivery using the RED system were comparable with those of a commercial ketoprofen patch formulation. Thus, the RED system can be a potential topical and transdermal delivery system for various poorly bioavailable pharmaceuticals including HA, vitamin C, and lopinavir.     

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.     

Ultrasound Mediated Transdermal Insulin Delivery in Pigs Using a Lightweight Transducer

Purpose In previous studies, ultrasound mediated transdermal drug delivery has shown a promising potential as a method for noninvasive drug administration. For prospective future human application, this study was designed to determine the feasibility of lightweight cymbal transducer array as a practical device for noninvasive transdermal insulin delivery in large pigs. Materials and Methods Six Yorkshire pigs (100–140 lbs) were divided into two groups. As the control (n = 3), the first group did not receive any ultrasound exposure with the insulin. The second group (n = 3) was treated with ultrasound and insulin at 20 kHz with an I_sptp = 100 mW/cm² at a 20% duty cycle for 60 min. With the pigs in lateral recumbency after anesthesia, the ultrasound transducer with insulin was placed on the axillary area of the pig. At the beginning and every 15 min up to 90 min, the blood glucose level was determined using a glucose monitoring system. To compare the results of individual animals, the change of blood glucose level was normalized to each animal’s initial glucose value at the start of the experiment. Results Although each animal had a different initial glucose level, the mean and standard error for the six animals was 146 ± 13 mg/dl. For the control group, the blood glucose level increased to 31 ± 21 mg/dl compared to the initial baseline over the 90 min experiment. However for the ultrasound with insulin treated group, the glucose level decreased to −72 ± 5 mg/dl at 60 min (p <  0.05) and continued to decrease to −91 ± 23 mg/dl in 90 min (p < 0.05). Conclusion The results indicate the feasibility of ultrasound mediated transdermal insulin delivery using the cymbal transducer array in animal with a similar size and weight to a human. Based on these result, the cymbal array has potential as a practical ultrasound system for noninvasive transdermal insulin delivery for diabetes management.     

Noninvasive delivery of a novel inotropic catecholamine: iontophoretic versus intravenous infusion in dogs

Using a newly developed iontophoretic delivery device, a novel inotropic catecholamine, pharmacologically similar to dobutamine, has been successfully administered to dogs by noninvasive transdermal infusion for periods of up to 1.5 h. The technique was compared with intravenous infusion and shown to be capable of achieving the same degree of cardiac contractility and steady-state plasma concentrations of the inotrope. There was also a good linear relationship between the applied current and the resulting steady-state plasma concentrations of the inotrope. Approximately 2 mA of applied current during transdermal iontophoresis produced a response equivalent to an intravenous infusion of 1 micrograms/kg/min of the drug.     

微针透皮给药系统应用研究进展

微针透皮给药系统是近年来透皮给药系统研究的热点。微针透皮给药系统具有注射给药和透皮给药的双重优势,具有快速、方便、无痛等众多优点,研究表明可以显著提高药物透皮速率和吸收量,特别是在蛋白质、多肽、DNA和RNA等大分子物质的透皮制剂研究领域表现出良好的效果和应用前景,本文对微针透皮给药系统应用研究的最新进展进行了综述。随着微针加工技术、载药技术和应用研究的不断深入,微针透皮技术在临床领域将会有更广泛的应用。     

Experimental design for optimizing drug release from silicone elastomer matrix and investigation of transdermal drug delivery

Silicone elastomers are commonly used for medical devices and external prosthesis. Recently, there has been growing interest in silicone-based medical devices with enhanced function that release drugs from the elastomer matrix. In the current study, an experimental design approach was used to optimize the release properties of the model drug diclofenac from medical silicone elastomer matrix, including a combination of four permeation enhancers as additives and allowing for constraints in the properties of the material. The D-optimal design included six factors and five responses describing material properties and release of the drug. The first experimental object was screening, to investigate the main and interaction effects, based on 29 experiments. All excipients had a significant effect and were therefore included in the optimization, which also allowed the possible contribution of quadratic terms to the model and was based on 38 experiments. Screening and optimization of release and material properties resulted in the production of two optimized silicone membranes, which were tested for transdermal delivery. The results confirmed the validity of the model for the optimized membranes that were used for further testing for transdermal drug delivery through heat-separated human skin. The optimization resulted in an excipient/drug/silicone composition that resulted in a cured elastomer with good tensile strength and a 4- to 7-fold transdermal delivery increase relative to elastomer that did not contain excipients.     

青藤碱透皮贴剂定位给药传递能力的评价

目的评价青藤碱压敏胶分散型透皮贴剂的定位给药传递能力。方法通过经皮和经口两种给药途径的比较,采用小鼠局部组织分布研究评价青藤碱透皮贴剂的定位给药传递能力。结果与经口给药组相比,青藤碱的浓度在小鼠经皮给药组贴敷贴剂处的肌肉中更加平稳,而且肌肉-血浆浓度比更高。结论将青藤碱透皮贴剂应用于关节炎患病区域,可以定位传递药物至病灶部位,是一种更适宜的给药途径。     

Transdermal iontophoresis: impact on skin integrity as evaluated by various methods

Transdermal iontophoresis, a noninvasive technique that facilitates drug transport through the skin by the use of an external electrical field, has expanded the scope of drugs that can be delivered transdermally and enables programmable drug delivery. In general, transdermal iontophoresis is considered to be a safe procedure, associated with moderate erythema and tingling sensations. However, ensuring that the skin barrier maintains its integrity during iontophoresis is an essential factor to increase its clinical applicability. This review focuses on the effect of transdermal iontophoresis on the integrity of skin, as evaluated by impedance spectroscopy, microscopy, differential scanning calorimetry, infrared spectroscopy, X-ray diffraction, transepidermal water loss, laser doppler velocimetry, visual scoring, chromameter readings, and patient evaluation studies.     

混合胶团增溶的环孢素A经小鼠皮肤的渗透作用

目的研究由不同表面活性剂和磷脂所组成的混合胶团(mixedmicelles)对环孢素A经小鼠皮肤给药的渗透促进作用。方法将含药混合胶团溶液封闭性应用于离体或在体小鼠皮肤,测定接收介质和血液中环孢素A含量。结果离体条件下,不同表面活性剂和磷脂所形成的混合胶团的皮肤渗透作用强度为:胆酸钠-磷脂混合胶团>脱氧胆酸钠-磷脂混合胶团>TritonX-100-磷脂混合胶团>Tween-20-磷脂混合胶团。在体条件下,用胆酸钠-磷脂混合胶团后,5h血药浓度达峰值,随后血药浓度缓慢下降。结论混合胶团在水溶液状态下对大分子难溶药物环孢素A具有一定的皮肤促渗效果。     

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。     

Permeation enhancer strategies in transdermal drug delivery

Abstract

Today, ～74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.     

Transdermal iontophoresis. Part II: Peptide and protein delivery.

The advent of sophisticated biotechnological processes has generated an interest in peptide and protein pharmaceuticals. However, the rapid developments in biotechnology are not matched by the developments in the delivery of these molecules. Presently, most of the peptides and proteins are delivered by parenteral route due to their poor oral bioavailability. The inherent discomforts associated with the parenteral therapy has prompted investigations into other nonparenteral routes and drug delivery techniques. Transdermal iontophoresis is one such technique showing good promise in the controlled and enhanced delivery of peptides and proteins. It offers noninvasive, continuous, pulsatile delivery as well as preprogramed complex dosing regimens. Miniature battery powered and wearable patches for peptides and proteins are expected to be on the market by the turn of this century. In continuation of our earlier review, this review explores the potential of transdermal iontophoresis for the delivery of peptides and proteins with the main focus on the suitability of the technique along with the factors to be considered in the design of this drug delivery system and its future prospects.     

纳米药物载体在经皮给药系统中应用的研究进展

目的介绍纳米药物载体在经皮给药系统中的应用。方法查阅国内外文献共31篇,从纳米药物载体在经皮给药系统中的应用及各自的优势和不足等方面进行综述。结果纳米药物载体具有提高药物的化学稳定性、促进药物经皮吸收、控制药物释放以及定位给药等优点,在药物的经皮吸收方面具有广阔应用前景。结论纳米药物载体为药物的经皮通透提供了新的途径和方法,但是其安全性和有效性仍需进一步研究。     

脂质体经皮给药研究进展

目的：分析总结近年来国外脂质体经皮或黏膜给药研究的特点和应用进展。方法：对近年来脂质体药物特点，主要对在皮肤疾病和美容方面，对局部伤口的治疗，在皮肤损伤和保护中的应用，在眼科疾病中的应用进行综述。结果与结论：脂质体是一种很好的定向药物载体，它的应用将越来越广。     

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.