Two-photon polymerization of microneedles for transdermal drug delivery

Abstract

Importance of the field-Microneedles are small-scale devices that are finding use for transdermal delivery of protein-based pharmacologic agents and nucleic acid-based pharmacologic agents; however, microneedles prepared using conventional microelectronics-based technologies have several shortcomings, which have limited translation of these devices into widespread clinical use.Areas covered in this review-Two photon polymerization is a laser-based rapid prototyping technique that has been recently used for direct fabrication of hollow microneedles with a wide variety of geometries. In addition, an indirect rapid prototyping method that involves two photon polymerization and polydimethyl siloxane micromolding has been used for fabrication of solid microneedles with exceptional mechanical properties.What the reader will gain-In this review, the use of two photon polymerization for fabricating in-plane and out-of-plane hollow microneedle arrays is described. The use of two photon polymerization-micromolding for fabrication of solid microneedles is also reviewed. In addition, fabrication of microneedles with antimicrobial properties is discussed; antimicrobial microneedles may reduce the risk of infection associated with formation of channels through the stratum corneum.Take home message-It is anticipated that the use of two photon polymerization as well as two photon polymerization-micromolding for fabrication of microneedles and other microstructured drug delivery devices will increase over the coming years. Declaration of interestThe authors state no conflicts of interest and have received no payment in the preparation of this manuscript. NIH Public Access Overview of the MarketNucleic acid-and protein-based pharmacologic agents are finding greater use in the treatment of cancer, diabetes mellitus, and other chronic medical conditions. Oral, sublingual, or rectal delivery are the most appealing routes of administration due to the fact that doses can be administered by the patient. In addition, no painful or complicated techniques are necessary [1]. Unfortunately, many nucleic acid-and protein-based pharmacologic agents cannot be administered in enteral form due to pH driven molecular degradation or first-pass metabolism by the liver [2]. Transdermal patches have found increasing use in recent years for delivery of hormones (e.g., estrogen), analgesic agents (e.g., fentanyl), as well as various other pharmacologic agents; however, charged, polar, or large pharmacological agents cannot be delivered using transdermal patches because these agents cannot pass through an intact stratum corneum [3][4][5]. The stratum corneum is the outermost 15 µm thick layer of the epidermis, which contains nonviable keratinized cells and serves as a barrier to pharmacologic agent transport [6]. Transport of pharmacologic agents through the stratum corneum may be enhanced through the use of chemical penetration enhancers, electroporation, iontophoresis, and sonophoresis; however, these techniques have not seen widespread clin...

Microneedles for drug delivery: trends and progress

“…The use of MN as a DD system is an important development as the potential to allow a wider scope of molecules to be transdermally delivered through the skin is greatly increased (Dhamech et al, 2010;Gittard et al, 2010;Milewski et al, 2010;Singh et al, 2010). The amount of drug that is delivered can also be increased.…”

Laser Engineering of Surface Structures

“…These devices are used to create pores in the 15-μm thick stratum corneum layer of the skin, enabling transdermal delivery of pharmacologic agents and vaccines. Microneedles with complex shapes, including in-plane hollow microneedles, out-of-plane hollow microneedles and mosquito fascicle-shaped microneedles, have been created out of organically modified ceramic materials using two-photon polymerization [107][108][109]. These studies showed that microneedle design may be rapidly tailored for specific medical applications using two-photon polymerization.…”

An array of individually addressable micro-needles for mapping pH distributions

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Silicon has been used predominantly for fabrication of microneedles, however the fragility and the cost of the microfabrication process are major drawbacks for this material. [1][2][3][4] Injection molding has instead emerged as an alternative fabrication process offering advantages such as cost and robustness.…”