title: Microneedles and other physical methods for overcoming the stratum corneum barrier for cutaneous gene therapy.
abstract: 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.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3XF, UK.
authors.forename: Sion
authors.initials: S
authors.lastname: Coulman
authors.forename: Chris
authors.initials: C
authors.lastname: Allender
authors.forename: James
authors.initials: J
authors.lastname: Birchall
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D004817:Epidermis / Q000033:anatomy & histology / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007271:Injections, Intradermal; D008845:Microinjections / Q000295:instrumentation* / Q000379:methods; D008953:Models, Anatomic; D009339:Needles / Q000592:standards*