Brown Marc B, Martin Gary P, Jones Stuart A, Akomeah Franklin K
Pharmaceutical Sciences Research Division, King's College London and MedPharm Ltd., London, United Kingdom.
Drug Deliv. 2006 May-Jun;13(3):175-87. doi: 10.1080/10717540500455975.
The protective function of human skin imposes 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 adequate lipophilicity and also a molecular weight <500 Da. These requirements have limited the number of commercially available products based on transdermal or dermal delivery. Various strategies have emerged over recent years to optimize delivery and these can be categorized into passive and active methods. The passive approach entails the optimization of formulation or drug carrying vehicle to increase skin permeability. Passive methods, however do not greatly improve the permeation of drugs with molecular weights >500 Da. In contrast active methods that normally involve physical or mechanical methods of enhancing delivery have been shown to be generally superior. Improved delivery has been shown for drugs of differing lipophilicity and molecular weight including proteins, peptides, and oligonucletides using electrical methods (iontophoresis, electroporation), mechanical (abrasion, ablation, perforation), and other energy-related techniques such as ultrasound and needless injection. 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 article provides a detailed review of the next generation of active delivery technologies.
人体皮肤的保护功能对能够穿过屏障的渗透物类型施加了物理化学限制。药物要通过皮肤被动给药,需要具有足够的亲脂性,并且分子量<500 Da。这些要求限制了基于透皮或真皮给药的市售产品数量。近年来出现了各种优化给药的策略,这些策略可分为被动和主动方法。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,被动方法并不能显著提高分子量>500 Da的药物的渗透性。相比之下,通常涉及增强给药的物理或机械方法的主动方法已被证明总体上更具优势。使用电方法(离子电渗法、电穿孔法)、机械方法(磨皮、消融、穿孔)以及其他与能量相关的技术(如超声和无针注射),已证明不同亲脂性和分子量的药物(包括蛋白质、肽和寡核苷酸)的给药得到了改善。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与安全性、有效性、操作简便性和成本效益。本文对下一代主动给药技术进行了详细综述。