Study of Polymeric Microneedle Arrays for Drug Delivery
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Study of Polymeric Microneedle Arrays for Drug Delivery Aleksandr Ovsianikov1, Anand Doraiswamy2, Roger Narayan2, and Boris N. Chichkov1 1 Laser Zentrum Hannover e.V., Hollerithallee 8, Hannover, 30419, Germany 2 University of North Carolina, Chapel Hill, NC, 27599-7575
ABSTRACT Two-photon polymerization (2PP) is a novel technology for the fabrication of complex threedimensional (3D) microstructures. The number of applications employing this technology is rapidly increasing, and includes the fabrication of three-dimensional photonic crystals [1-4], medical devices[5, 6], and scaffolds for tissue engineering [7]. We have used two-photon polymerization to fabricate microneedle arrays with various geometries. These devices provide a unique approach for transdermal delivery of nucleic acid- and protein-based pharmacologic agents. Many issues associated with conventional intravenous drug administration, including pain to the patient, trauma at the injection site, and difficulty in providing sustained release of a pharmacological agent, may be eliminated by applying the microneedles. The effect of microneedle geometry (e.g., tip sharpness and aspect ratio) on porcine adipose tissue penetration was examined. Our results indicate that microneedles created using the 2PP technique are suitable for in vivo use, and integration with next generation MEMS- and NEMS-based drug delivery devices. INTRODUCTION Transdermal drug delivery is a method that has experienced a rapid development in the past two decades, and has often shown improved efficiency over the other delivery routes [8]. It avoids many issues associated with intravenous drug administration, including pain to the patient, trauma at the injection site, and difficulty in providing sustained release of pharmacologic agents. In addition precise dosing, safety, and convenience are addressed by transdermal drug delivery. Nevertheless, only a small number of pharmacological substances are delivered in this manner today. The main reason for that is the significant barrier to diffusion provided by the upper layers of the skin. The top layer, called stratum corneum, is composed of dead cells surrounded by lipid. This layer provides the most significant barrier to diffusion to approximately 90% of transdermal drug applications [9, 10]. A few techniques, enhancing the substance delivery through the skin have been proposed. Two of the better-known active technologies are iontophoresis and sonophoresis. The rate of product development involving these technologies has been relatively slow [11, 12]. This is partly conditioned by the relative complexity of the resulting systems, compared to passive transdermal systems. Micro-needle enhanced drug delivery is a novel passive technology. These systems use arrays of hollow or solid microneedles to open pores in the upper layer of the skin and assist drug transportation. The length of the needles is chosen such that they do not penetrate into the dermis, pervaded with nerve endings, and thus do not cause pain. In order to pene
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