Coulman Sion, Allender Chris, Birchall James
Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3XF, UK.
Crit Rev Ther Drug Carrier Syst. 2006;23(3):205-58. doi: 10.1615/critrevtherdrugcarriersyst.v23.i3.20.
The outermost layer of skin, the epidermis, has developed formidable physical and immunological barrier properties that prevent infiltration of deleterious chemicals and pathogens. Consequently, transdermal delivery of medicaments is currently restricted to a limited number of low molecular weight drugs. As a corollary, there has been significant recent interest in providing strategies that disrupt or circumvent the principal physical barrier, the stratum corneum, for the efficient cutaneous delivery of macromolecular and nucleic acid based therapeutics. These strategies include: electrical methods, intradermal injection, follicular delivery, particle acceleration, laser ablation, radiofrequency ablation, microscission, and microneedles. The application of microfabricated microneedle arrays to skin creates transient pathways to enable transcutaneous delivery of drugs and macromolecules. Microneedle use is simple, pain-free, and causes no bleeding, with further advantages of convenient manufacture, distribution, and disposal. To date, microneedles have been shown to deliver drug, peptide, antigen, and DNA efficiently through skin. Robust and efficient microneedle designs and compositions can be inserted into the skin without fracture. Further progress in microneedle array design, microneedle application apparatus, and integrated formulation will confirm this methodology as a realistic clinical strategy for delivering a range of medicaments, including DNA, to and through skin.
皮肤的最外层,即表皮,已形成强大的物理和免疫屏障特性,可防止有害化学物质和病原体的侵入。因此,目前经皮给药仅限于少数低分子量药物。相应地,最近人们对提供破坏或规避主要物理屏障即角质层的策略产生了浓厚兴趣,以便有效地经皮递送基于大分子和核酸的治疗药物。这些策略包括:电方法、皮内注射、毛囊递送、粒子加速、激光消融、射频消融、微切割和微针。将微制造的微针阵列应用于皮肤可创建瞬时通道,以实现药物和大分子的经皮递送。微针使用简单、无痛且不引起出血,还具有制造、分发和处置方便的进一步优点。迄今为止,微针已被证明能有效地通过皮肤递送药物、肽、抗原和DNA。坚固且高效的微针设计和成分可插入皮肤而不折断。微针阵列设计、微针应用装置和整合制剂方面的进一步进展将证实这种方法是一种切实可行的临床策略,可用于将包括DNA在内的一系列药物递送至皮肤并透过皮肤。