Brown Marc B, Traynor Matthew J, Martin Gary P, Akomeah Franklin K
School of Pharmacy, University of Hertfordshire, College Lane Campus, Hatfield, Herts., UK.
Methods Mol Biol. 2008;437:119-39. doi: 10.1007/978-1-59745-210-6_5.
Human skin serves a protective function by imposing physicochemical limitations to the type of permeant that can traverse the barrier. For a drug to be delivered passively via the skin it needs to have a suitable lipophilicity and a molecular weight < 500 Da. The number of commercially available products based on transdermal or dermal delivery has been limited by these requirements. In recent years various passive and active strategies have emerged to optimize delivery. The passive approach entails the optimization of formulation or drug carrying vehicle to increase skin permeability. However, passive methods do not greatly improve the permeation of drugs with molecular weights >500 Da. In contrast, active methods, normally involving physical or mechanical methods of enhancing delivery, have been shown to be generally superior. The delivery of drugs of differing lipophilicity and molecular weight, including proteins, peptides and oligonucletides, has been shown to be improved by active methods such as iontophoresis, electroporation, mechanical perturbation and other energy-related techniques such as ultrasound and needleless injection. This chapter details one practical example of an active skin abrasion device to demonstrate the success of such active methods. The in vitro permeation of acyclovir through human epidermal membrane using a rotating brush abrasion device was compared with acyclovir delivery using iontophoresis. It was found that application of brush treatment for 10 s at a pressure of 300 N m(-2) was comparable to 10 min of iontophoresis. The observed enhancement of permeability observed using the rotating brush was a result of disruption of the cells of the stratum corneum, causing a reduction of the barrier function of the skin. However, for these novel delivery methods to succeed and compete with those already on the market, the prime issues that require consideration include device design and safety, efficacy, ease of handling, and cost-effectiveness. This chapter provides a detailed review of the next generation of active delivery technologies.
人体皮肤通过对可穿过屏障的渗透物类型施加物理化学限制来发挥保护作用。药物要通过皮肤被动给药，需要具有合适的亲脂性且分子量<500 Da。基于透皮或真皮给药的市售产品数量受到这些要求的限制。近年来，出现了各种被动和主动策略来优化给药。被动方法需要优化制剂或药物载体以增加皮肤渗透性。然而，被动方法并不能大大提高分子量>500 Da的药物的渗透性。相比之下，主动方法通常涉及增强给药的物理或机械方法，已被证明总体上更具优势。离子电渗、电穿孔、机械扰动以及超声和无针注射等其他与能量相关的技术等主动方法已被证明可改善不同亲脂性和分子量的药物（包括蛋白质、肽和寡核苷酸）的给药。本章详细介绍了一种主动皮肤磨损装置的实际示例，以证明此类主动方法的成功。使用旋转刷磨损装置将阿昔洛韦通过人表皮膜的体外渗透性与使用离子电渗法的阿昔洛韦给药进行了比较。结果发现，在300 N m(-2)的压力下进行10 s的刷处理与10 min的离子电渗相当。使用旋转刷观察到的渗透性增强是角质形成细胞破坏的结果，导致皮肤屏障功能降低。然而，要使这些新型给药方法取得成功并与市场上现有的方法竞争，需要考虑的主要问题包括装置设计和安全性、有效性、易于操作以及成本效益。本章对下一代主动给药技术进行了详细综述。
