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.     

皮肤给药的经皮吸收与测量技术研究进展

经皮给药系统（TDDS）可避免首关效应、胃肠道破坏,为新型皮肤给药系统,可通过控制释放而延长治疗效果,成为药物制剂开发研究的热点之一。但是,药物的理化性质以及皮肤屏障影响药物的经皮吸收。综述了TDDS常用的促渗透技术,包括化学、物理、纳米、天然促渗透技术;介绍了促渗透能力的测定方法,包括体外、离体和体内评估皮肤渗透性的方法。通过对经皮药物递送系统和经皮吸收能力测定方法的归纳与总结,以期为TDDS的合理使用和快速发展提供参考。     

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.     

Potentials of new nanocarriers for dermal and transdermal drug delivery

Nanocarriers (NCs) are colloidal systems having structures below a particle or droplet size of 500 nm. In the previous years, the focus for the application of NCs was primarily placed on the parenteral and oral application. However, NCs applied to the skin are in the center of attention and are expected to be increasingly applied as the skin offers a lot of advantages for the administration of such systems. For the use of NCs to the skin, one has to differentiate between the desired effects: the local effect within the skin (dermal drug delivery) or a systemic effect accompanied by the permeation through the skin (transdermal drug delivery).Both for dermal and transdermal drug delivery, the stratum corneum (SC), the main barrier of the skin, has to be overcome.SC is one of the tightest barriers of the human body. Therefore, it is the primary goal of new NC to overcome this protective and effective barrier. For that purpose, new NCs such as microemulsions, vesicular (liposomes) and nanoparticular NCs are developed and investigated. This article evaluates the potentials of these NCs for dermal and transdermal drug delivery.     

Microstructured bicontinuous phase formulations: their characterization and application in dermal and transdermal drug delivery

Introduction: The development of approaches to increase drug solubility and partitioning into the skin is an active area of research in topical and transdermal delivery. In addition to forming spherical aggregates, e.g., conventional oil in water or water in oil microemulsions, the combination of an oil, surfactant and water can create bicontinuous structures where the self-assembly properties of surfactants mean that the boundaries between oil and water are no longer random. This leads to the formation of specific microstructures whose intrinsic properties and interactions with the drug will determine the ability to formulate a given drug, its stability once formulated and its subsequent delivery.

Areas covered: The review explores the relationship between the microstructure of biphasic formulations, present in microemulsions and liquid crystalline phases, and drug delivery into the skin. An overview of possible internal microstructures is followed by a summary of the methods used for structure characterization. The final section presents the work to-date and discusses the efficacy of such vehicles in enhancing dermal and transdermal delivery.

Expert opinion: The combination of water, surface agent and oil generates a broad range of three dimensional structures differing in both chemical and physical proprieties. Knowledge of the microstructure is important in understanding the behavior of a formulation and its effect on drug delivery into the skin. Microstructure complexity, interactions between the drug and the vehicle (i.e., location and mobility) and those between the vehicle and the skin are key determinants of drug delivery.     

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。     

Hydrogels with smart systems for delivery of hydrophobic drugs

Introduction: Smart hydrogel systems present opportunities to not only provide hydrophobic molecule encapsulation capability but to also respond to specific delivery routes.

Areas covered: An overview of the design principles, preparation methods and applications of hydrogel systems for delivery of hydrophobic drugs is given. It begins with a summary of the advantages of hydrogels as delivery vehicles over other approaches, particularly macromolecular nanocarriers, before proceeding to address the design and preparation strategies and chemistry involved, with a particular focus on the introduction of hydrophobic domains into (naturally) hydrophilic hydrogels. Finally, the applications in different delivery routes are discussed.

Expert opinion: Modifications to conventional hydrogels can endow them with the capability to carry hydrophobic drugs but other functions as well, such as the improved mechanical stability, which is important for long-term in vivo residence and/or self-healing properties useful for injectable delivery pathways. These modifications harness hydrophobic-hydrophobic forces, physical interactions and inclusion complexes. The lack of in-depth understanding of these interactions, currently limits more delicate and application-oriented designs. Increased efforts are needed in (i) understanding the interplay of gel formation and simultaneous drug loading; (ii) improving hydrogel systems with respect to their biosafety; and (iii) control over release mechanism and profile.     

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。     

Chitosan and its derivatives as vehicles for drug delivery

Abstract

Chitosan and its derivatives as vehicles for drug delivery can achieve the purpose of sustained release and controlled release for drugs, improve the stability of drugs, and reduce adverse drug reactions. So, the bioavailability of drugs can be enhanced. Therefore, chitosan and its derivatives have become a hotspot in the field of drug delivery. Their characteristics as drug delivery vectors were introduced, the types and applications were summarized. The development direction of chitosan and its derivatives in this field was also forecasted.     

Trypsin as a novel potential absorption enhancer for improving the transdermal delivery of macromolecules

Objectives The aim was to assess the effect of trypsin on the transdermal delivery of macromolecules by applying its specific biochemical properties to the stratum corneum of the skin. Methods Fluorescein isothiocyanate (FITC)‐labelled dextrans (FDs), with molecular weights of 4 to 250 kDa, and FITC‐insulin were used as model macromolecules and a model polypeptide, and the in‐vitro transdermal permeation experiments, with or without trypsin (0.1–2.5%), were carried out using rat skin and cultured human epidermis. The mechanism for the enhancement of trypsin was also studied using fluorescence and conventional light microscopy. Key findings Trypsin significantly increased the transdermal permeability of all FDs through the rat skin (2.0‐ to 10.0‐fold). It also markedly enhanced the permeation of FD4 through three‐dimensional cultured human epidermis (3.1‐fold), which was used to evaluate the transport pathways other than the transfollicular route. Furthermore, the permeation flux of FITC‐insulin was increased by 10.0‐fold with trypsin pretreatment (from 0.02 ± 0.00 to 0.20 ± 0.07 μg/cm² per h). Mechanistic studies indicated that trypsin affects both the intercellular pathway and the hair follicular route, and may alter stratum corneum protein structures, thereby affecting skin barrier properties. Conclusions This study suggests that trypsin could be effective as a biochemical enhancer for the transdermal delivery of macromolecules including peptide and protein drugs.     

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...     

Two-photon polymerization of microneedles for transdermal drug delivery

Importance of the field: Microneedles are small-scale devices that are finding use for transdermal delivery of protein-based pharmacologic agents and nucleic acid-based pharmacologic agents; however, microneedles prepared using conventional microelectronics-based technologies have several shortcomings, which have limited translation of these devices into widespread clinical use.

Areas covered in this review: Two-photon polymerization is a laser-based rapid prototyping technique that has been used recently for direct fabrication of hollow microneedles with a wide variety of geometries. In addition, an indirect rapid prototyping method that involves two-photon polymerization and polydimethyl siloxane micromolding has been used for fabrication of solid microneedles with exceptional mechanical properties.

What the reader will gain: In this review, the use of two-photon polymerization for fabricating in-plane and out-of-plane hollow microneedle arrays is described. The use of two-photon polymerization-micromolding for fabrication of solid microneedles is also reviewed. In addition, fabrication of microneedles with antimicrobial properties is discussed; antimicrobial microneedles may reduce the risk of infection associated with the formation of channels through the stratum corneum.

Take home message: It is anticipated that the use of two-photon polymerization as well as two-photon polymerization-micromolding for fabrication of microneedles and other microstructured drug delivery devices will increase over the coming years.     

The importance of minipigs in dermal safety assessment: an overview

The use of miniature swine as a non-rodent species in safety assessment has continued to expand for over a decade and their use has become routine, particularly in pharmacology as a model for human integumentary diseases. Translational preclinical swine study data are now favorably compared and contrasted to human data, and miniature swine models provide important information in dermal safety assessment and skin pharmacology. For example, the miniature swine model has been well-accepted for cutaneous absorption and toxicity studies due to swine integument being morphologically and functionally similar to human skin. Subsequently, this model is important to dermal drug development programs, and it is the animal model of choice for assessment of dermal absorption, local tolerance and systemic toxicity following dermal exposures. In conclusion, the miniature swine model has an important role to play in the safety assessment of pharmaceutical products and in multiple aspects of human dermal drug development.     

Fluorocarbon nanoparticles as multifunctional drug delivery vehicles

The history and current status of fluorocarbon nanoparticles in biomedicine is briefly reviewed. The deficiencies of current fluorocarbon nanoparticle formulations are highlighted. Strategies to remedy such deficiencies and to functionalize fluorocarbon nanoparticles are presented. Potential applications of fluorocarbon nanoparticles as multifunctional drug delivery vehicles are discussed. The strength of fluorocarbon nanoparticles as drug delivery vehicles is that they integrate drug delivery with non-invasive MR imaging so that the biodistribution of the pharmaceutical entity (drug+delivery vehicle) can be monitored in real time. This, in turn, permits the physician to adjust treatment plan for each patient based on his/her actual response to the ongoing treatment.     

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.     

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,它的应用范围将越来越广     

Vesicular carriers for dermal drug delivery

The skin can offer several advantages as a route of drug administration although its barrier nature makes it difficult for most drugs to penetrate into and permeate through it. During the past decades there has been a lot of interest in lipid vesicles as a tool to improve drug topical delivery. Vesicular systems such as liposomes, niosomes, ethosomes and elastic, deformable vesicles provide an alternative for improved skin drug delivery. The function of vesicles as topical delivery systems is controversial with variable effects being reported in relation to the type of vesicles and their composition. In fact, vesicles can act as drug carriers controlling active release; they can provide a localized depot in the skin for dermally active compounds and enhance transdermal drug delivery. A wide variety of lipids and surfactants can be used to prepare vesicles, which are commonly composed of phospholipids (liposomes) or non-ionic surfactants (niosomes). Vesicle composition and preparation method influence their physicochemical properties (size, charge, lamellarity, thermodynamic state, deformability) and therefore their efficacy as drug delivery systems. A review of vesicle value in localizing drugs within the skin at the site of action will be provided with emphasis on their potential mechanism of action.     

多肽蛋白质类药物离子导入经皮给药的研究进展

论述了多肽蛋白质类药物离子导入经皮给药的特点及主要影响因素,重点介绍了近年来国际上对胰岛素、降血钙素、促黄体(生成)激素释放激素、精氨酸抗利尿激素(加压素)等多肽蛋白质类药物离子导入经皮给药的研究进展.     

Evaluation of proniosomes as an alternative strategy to optimize piroxicam transdermal delivery

The current investigation aims to evaluate the transdermal potential of niosomes bearing a potent non-steroidal anti-inflammatory, piroxicam. Piroxicam-loaded niosomes were prepared and characterized for surface morphology, entrapment efficiency and in vitro permeation across excised rat skin from various proniosome gel formulations using Franz diffusion cells. Various non-ionic surfactants were used to achieve optimum encapsulation efficiency. The prepared proniosomes significantly improved drug permeation and reduced the lag time (p < 0.05). Proniosomes prepared with Span 60 provided a higher piroxicam flux across the skin than did those prepared with Tween 80. Niosomes prepared using Span 60 showed a higher release rate than those prepared using non-ionic surfactants, Span 20 and Span 80, while those prepared from Tween showed higher release rate than formula prepared with Span. This indicates that lipophilicity and hydrophilicity of surfactant has a main role in release rates of piroxicam. Particle size of piroxicam niosomal vesicles formed by proniosome was determined by scanning electron microscopy. The encapsulation efficiency was evaluated by a specific high performance liquid chromatography method. Niosomes formed from using Spans and Tweens exhibited very high encapsulation efficiency. The results are very encouraging and suggest that niosomes can act as promising carriers offering an alternative approach for transdermal delivery of piroxicam.