Atom sharp microneedles , the missing link in microneedle drug delivery ?

Introduction The skin barrier function is a major challenge for delivery of drugs via the skin. Located in the outermost layer of the skin, the stratum corneum (SC) consists of dead cells embedded in lipid regions, only 10–20 µm thick, tough but flexible and elastic. Hypodermic needles penetrate the skin succesfully, but nerve rich tissue in the lower skin is penetrated which is simply painfull. Minimally invasive micro-needles provide a reduction of pain sensation. Pain can be eliminated completely when drugs, like vaccins or insuline, are delivered into the dermis, some 0.1 to 1 mm under the stratum corneum. [1]. This shallow penetration is no practice today since hypodermic needles need to have long bevelled tips to ease penetration. Since a significant percentage of the people suffer from needle-phobia, the holy grail is a micro-needle that delivers drugs into the dermis and therefore is not felt (and is not seen either). Micro-needles are small, and to obtain an acceptable drug flow rates through the inner bores, more needles on a device aerea are used, an approach not used in the needle practice today. Micro-needles have been researched for many decades, however since bulk and surface micromachining of silicon became available during the 1990s and made microstructuring possible, the number of different needle designs increased and real interest rose worldwide [2]. As a result of these fabrication techniques, and the fact that in the early days of micro-needles, needle were designed very short, most designs have been out-of-plane of plane needles. These have been tested in vitro and some on human tissue or in vivo, with various results [3]. Some results have been published [4], but also many results stay unpublished: it has become clear the out-of-plane needles are of use in some application areas, but trouble-free application is not there yet. The issues with out-of-plane needle designs have not been reported widely. By studying the publications and by interpretation of the results in combination with the various designs, one unresolved issue becomes very clear: sharpness. Since a micro-needle is supposed to be shorter than a hypodermic needle, the insertion in the elastic but tough statum corneum is not straight forward. When length is not compensated by extra sharpness, there simply is no skin penetration. All initial out-of-plane initiatives suffered from this shortcoming, especially since they also were relatively short. Since 2007 some improvements have been reported [5] : It has …