Microneedles

Park, J.-H., Allen, M.G. and Prausnitz, M.R. (2005) Biodegradable polymer microneedles fabrication, mechanics and transdermal drug delivery. Journal of Controlled Release, 104, 51-66. 

Furthermore, the radicals formed upon field-induced hydrogen abstraction can lead to polymerization products on the emitter surface. The mechanism of this field polymerization helped to elucidate the phenomenon of activation of field emitters, i.e., the growth of microneedles on the emitter surface under the conditions of field ionization of certain polar organic compounds. [59]... 

PAHs adsorbed on particles of carbon black were also photostabilized (Behymer and Hites, 1988). However, Barofsky and Baum (1976) demonstrated that BaP, anthracene, BaA, and pyrene deposited on carbon microneedle field desorption emitters and exposed to UV radiation were all photooxidized to carbonyl compounds. Similarly, PAHs can photodegrade efficiently in air when adsorbed to substrates of silica gel, alumina, or glass plates (e.g., see Lane and Katz, 1977 Kormacher et al., 1980 Behymer and Hites, 1985 Yokely et al., 1986). 

Cormier M, et al. Transdermal delivery of desmopressin using a coated microneedle array patch system. J Control Release 2004 97 503-511. 

Prausnitz M. Microneedles for transdermal drug delivery. Adv Drug Delivery Rev 2004 56 581-587. 

Henry S, McAllister D, Allen M, Prausnitz M. Microfabricated microneedles a novel approach to transdermal drug delivery. J Pharm Sci 1998 87 922-925. 

It is therefore desirable to devise strategies both to enhance the penetration of molecules, which can already breach the skin barricade passively to some extent, and also to widen the spectrum of drug molecules that can penetrate the skin at therapeutically beneficial doses. Many tactics have been utilized to help overcome the barrier function. These include chemical means (e.g., chemical penetration enhancers or entrapment of molecules within lipid vesicles) or physical methods (such as ultrasound, microneedles, or electrical methods). Two important electrical methods are iontophoresis and electroporation. 

Microneedle Structures Prepared from Other Materials.340... 

Microneedles, so termed as they commonly range from 100 to 1000 pm in length, are designed to perforate the stratum corneum thus providing a direct and controlled route of access to the underlying tissue layers. When inserted into the skin, microneedles create microscopic punctures through the stratum corneum and into the viable epidermis. The length of the microneedle is controlled to ensure that the depth of penetration does not... 

FIGURE 18.1 Schematic representation of the concept for microneedle-assisted delivery, (a) The microneedles penetrate the stratum corneum, to facilitate access of molecules to the viable epidermis, without impacting on the underlying nerve endings and blood vessels (b) when removed the microneedles have created conduits for drug delivery (c) hollow microneedles allow direct injection of the formulation. 

In collaboration with The Cardiff School of Engineering and Tyndall National Institute, Cork, our laboratories have characterized and exploited microneedles prepared using dry-and wet-etching methodologies. 

If skin is placed in a water bath under controlled conditions [14] the primary barrier to transdermal delivery, the epidermal membrane comprising the stratum corneum and viable epidermis, can be readily removed and used to analyze the penetration and diffusion of materials. Figure 18.3a and Figure 18.3b show the appearance of human breast epidermal membrane, with epidermis facing uppermost, following application of the cylindrical dry-etch and pyramidal wet-etch silicon microneedles, respectively. In each case the microneedles are clearly shown to pierce the stratum corneum and viable epidermis to facilitate controlled access of molecules to the target region of skin. 

FIGURE 18.2 Scanning electron micrographs of silicon microneedles, (a) Silicon microneedles micro-fabricated using a modified form of the BOSCH deep reactive ion etching process. The microfabrication process was accomplished at CCLRC Rutherford Appleton Laboratory (Chilton, Didcot, Oxon, UK). The wafer was prepared at the Cardiff School of Engineering, Cardiff University, UK. Bar = 100 pm (b-d) platinum-coated silicon microneedles prepared using a wet-etch microfabrication process performed at the Tyndall National Institute, Cork, Ireland. Bar = 1 mm (b), 100 pm (c,d). 

FIGURE 18.3 Scanning electron micrographs of epidermal membrane treated with dry-etch and wet-etch silicon microneedles. The epidermal membrane, consisting of stratum corneum and viable epidermis, was obtained by heat separation of full-thickness human breast skin. The tissue was immersed in distilled water preheated to 60°C for 60 s and the upper layers carefully peeled off from the dermal layer using tweezers. Epidermal membranes were treated with microneedles for 30 s at an approximate pressure of 2 kg/cm2. (a) Dry-etch microneedle-treated epidermal membrane. Bar = 200 pm (b) wet-etch microneedle-treated epidermal membrane. Bar = 500 pm. 

Whereas solid microneedle arrays present the opportunity to create conduits through the restrictive skin barrier layer, the application of the formulation into the channel through drycoating the microneedle array or coadministration of a solution, suspension, emulsion, or gel containing the medicament generally relies on passive delivery mechanisms. The capacity to microfabricate hollow microneedles, however, allows a controlled quantity of the medicament to be actively delivered from the tip of the inserted microneedle at a defined rate. In addition, hollow microneedles provide the opportunity to not only deliver substances but also to withdraw material from the skin for analysis, monitoring, and responsive purposes. 

A recent study used hollow microneedles with the following dimensions 20-100 pm in diameter and 100-150 pm in length to deliver insulin through skin [22]. In vivo tests in diabetic animals, however, were unable to demonstrate any functional delivery of insulin through the hollow microneedles. It is therefore essential that the engineering processes evolve to ensure that both microneedle length and tip sharpness are optimized for systemic drug delivery to be seen in vivo. 

---