ABSTRACT

Introduction .................................................................................................................................... 239 Microneedle Fabrication................................................................................................................. 240

Solid Silicon Microneedles ......................................................................................................... 240 Solid Metal Microneedles ........................................................................................................... 241 Solid Polymer Microneedles....................................................................................................... 242 Hollow Metal Microneedles ....................................................................................................... 244 Hollow Silicon Microneedles ..................................................................................................... 244

Microneedle Properties .................................................................................................................. 244 Insertion into Skin ...................................................................................................................... 244 Avoidance of Pain....................................................................................................................... 246

Transdermal Delivery Using Microneedles.................................................................................... 247 In Vitro Delivery of Model Compounds.................................................................................... 247 In Vivo Delivery of Peptides and Proteins ................................................................................ 249 In Vivo Delivery of Genetic Material ......................................................................................... 251

Discussion and Conclusions .......................................................................................................... 252 Manufacturing ............................................................................................................................. 252 Optimization of Microneedle Design......................................................................................... 252 Strengths and Limitations of Microneedles................................................................................ 253

References....................................................................................................................................... 254

Conventional drug delivery using pills or injection is often not suitable for new protein, DNA, and other therapies.1-3 An attractive alternative involves transdermal delivery from a patch, which avoids (i) degradation in the gastrointestinal tract and first-pass effects of the liver associated with oral delivery and (ii) the pain and inconvenience of intravenous injection.4-7 Delivery across skin also offers the possibility to continuously control the delivery rate, in contrast to conventional methods that deliver a large, discrete bolus. Despite these advantages, transdermal drug delivery is severely limited by the poor

permeability of human skin; most drugs do not cross skin at therapeutic rates. Chemical,8

electrical,9 ultrasonic,10 and other methods have been developed to increase rates of transdermal transport, but have made only limited clinical impact to date.