Effect of microneedle geometry and supporting substrate on microneedle array penetration into skin.

Microneedles are being fast recognized as a useful alternative to injections in delivering drugs, vaccines, and cosmetics transdermally. Owing to skin's inherent elastic properties, microneedles require an optimal geometry for skin penetration. In vitro studies, using rat skin to characterize microneedle penetration in vivo, require substrates with suitable mechanical properties to mimic human skin's subcutaneous tissues. We tested the effect of these two parameters on microneedle penetration. Geometry in terms of center-to-center spacing of needles was investigated for its effect on skin penetration, when placed on substrates of different hardness. Both hard (clay) and soft (polydimethylsiloxane, PDMS) substrates underneath rat skin and full-thickness pig skin were used as animal models and human skins were used as references. It was observed that there was an increase in percentage penetration with an increase in needle spacing. Microneedle penetration with PDMS as a support under stretched rat skin correlated better with that on full-thickness human skin, while penetration observed was higher when clay was used as a substrate. We showed optimal geometries for efficient penetration together with recommendation for a substrate that could better mimic the mechanical properties of human subcutaneous tissues, when using microneedles fabricated from poly(ethylene glycol)-based materials.

[1]  S. Liawruangrath,et al.  Simultaneous determination of tolperisone and lidocaine by high performance liquid chromatography. , 2001, Journal of pharmaceutical and biomedical analysis.

[2]  D. JamesConrad,et al.  マイクロ流体デバイスにおいて誘電泳動と磁気泳動を使用した高い効率の磁気粒子集合化 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター , 2010 .

[3]  Aleksandr Ovsianikov,et al.  The effects of geometry on skin penetration and failure of polymer microneedles , 2013, Journal of adhesion science and technology.

[4]  Diganta Bhusan Das,et al.  Optimizing Microneedle Arrays to Increase Skin Permeability for Transdermal Drug Delivery , 2009, Annals of the New York Academy of Sciences.

[5]  Clifton R. Johnston,et al.  Geometrical effects in mechanical characterizing of microneedle for biomedical applications , 2004 .

[6]  Septimiu E. Salcudean,et al.  Needle insertion modeling and simulation , 2003, IEEE Trans. Robotics Autom..

[7]  M. Másson,et al.  Investigation of drug-cyclodextrin complexes by a phase-distribution method: some theoretical and practical considerations. , 2005, Chemical & pharmaceutical bulletin.

[8]  H. Zahouani,et al.  In vivo skin biophysical behaviour and surface topography as a function of ageing. , 2013, Journal of the mechanical behavior of biomedical materials.

[9]  S. Dunne,et al.  Effect of Distance from Curing Light Tip to Restoration Surface on Depth of Cure of Composite Resin , 2008, Primary dental care : journal of the Faculty of General Dental Practitioners.

[10]  Thakur Raghu Raj Singh,et al.  Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[11]  Wijaya Martanto,et al.  Microinfusion Using Hollow Microneedles , 2006, Pharmaceutical Research.

[12]  Mark R Prausnitz,et al.  Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force. , 2004, Journal of biomechanics.

[13]  Diganta Bhusan Das,et al.  Optimization of square microneedle arrays for increasing drug permeability in skin , 2008 .

[14]  J. Bouwstra,et al.  Improved piercing of microneedle arrays in dermatomed human skin by an impact insertion method. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[15]  A. Fahr,et al.  Skin penetration enhancement by a microneedle device (Dermaroller) in vitro: dependency on needle size and applied formulation. , 2009, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[16]  Shekhar Bhansali,et al.  Sharpening of hollow silicon microneedles to reduce skin penetration force , 2010 .

[17]  Mark R. Prausnitz,et al.  Effect of Microneedle Design on Pain in Human Volunteers , 2008, The Clinical journal of pain.

[18]  Lifeng Kang,et al.  A simple method of microneedle array fabrication for transdermal drug delivery , 2013, Drug development and industrial pharmacy.

[20]  H. Zahouani,et al.  In vivo measurements of the elastic mechanical properties of human skin by indentation tests. , 2008, Medical engineering & physics.

[21]  Wijaya Martanto,et al.  Mechanism of fluid infusion during microneedle insertion and retraction. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[22]  Jung-Hwan Park,et al.  Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[23]  D. Das,et al.  Influence of array interspacing on the force required for successful microneedle skin penetration: theoretical and practical approaches. , 2013, Journal of pharmaceutical sciences.

[24]  Y. Kalia,et al.  TRANSDERMAL DRUG DELIVERY: Clinical Aspects , 1998 .

[25]  S. Talegaonkar,et al.  Chemical penetration enhancers: a patent review , 2009, Expert opinion on therapeutic patents.

[26]  Allison M. Okamura,et al.  Force modeling for needle insertion into soft tissue , 2004, IEEE Transactions on Biomedical Engineering.

[27]  Jung-Hwan Park,et al.  Microneedles for drug and vaccine delivery. , 2012, Advanced drug delivery reviews.

[28]  Jie Zhang,et al.  Evaluation needle length and density of microneedle arrays in the pretreatment of skin for transdermal drug delivery. , 2010, International journal of pharmaceutics.

[29]  Roger J Narayan,et al.  Indirect rapid prototyping of antibacterial acid anhydride copolymer microneedles , 2012, Biofabrication.

[30]  V. Nassehi,et al.  Modelling transdermal drug delivery using microneedles: effect of geometry on drug transport behaviour. , 2012, Journal of pharmaceutical sciences.