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Penetration-enhanced ultrasharp microneedles and prediction on skin interaction for efficient transdermal drug delivery
KTH, School of Electrical Engineering (EES), Microsystem Technology.
KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
KTH, School of Electrical Engineering (EES), Microsystem Technology.
KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
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2007 (English)In: Journal of microelectromechanical systems, ISSN 1057-7157, E-ISSN 1941-0158, Vol. 16, no 6, 1429-1440 p.Article in journal (Refereed) Published
Abstract [en]

This paper presents penetration-enhanced hollow microneedles and an analysis on the biomechanical interaction between microneedles and skin tissue. The aim of this paper is to fabricate microneedles that reliably penetrate the skin tissue without using penetration enhancers or special insertion tools that were used in the previous studies. The microneedles are made of silicon and feature ultrasharp tips and side openings. The microneedle chips were experimentally tested in vivo by injection of dye markers. To further investigate the penetration, the insertion progression and the insertion force were monitored by measuring the electrical impedance between microneedles and a counter electrode on the skin. The microneedle design was also tested using a novel simulation approach and compared to other previously published microneedle designs. The purpose of this specific part of the paper was to investigate the interaction mechanisms between a microneedle and the skin tissue. This investigation is used to predict how the skin deforms upon insertion and how microneedles can be used to create a leak-free liquid delivery into the skin. The fabricated microneedles successfully penetrated dry living human skin at all the tested sites. The insertion characteristic of the microneedle was superior to an earlier presented type, and the insertion force of a single microneedle was estimated to be below 10 mN. This low insertion force represents a significant improvement to earlier reported results and potentially allows a microneedle array with hundreds of needles to be inserted into tissue by hand.

Place, publisher, year, edition, pages
2007. Vol. 16, no 6, 1429-1440 p.
Keyword [en]
drug delivery, microneedles, skin modeling, transdermal
National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
URN: urn:nbn:se:kth:diva-7460DOI: 10.1109/JMEMS.2007.907461ISI: 000252012800016Scopus ID: 2-s2.0-36949000879OAI: oai:DiVA.org:kth-7460DiVA: diva2:12491
Note
QC 20100624Available from: 2007-09-10 Created: 2007-09-10 Last updated: 2011-11-03Bibliographically approved
In thesis
1. A Fully Integrated Microneedle-based Transdermal Drug Delivery System
Open this publication in new window or tab >>A Fully Integrated Microneedle-based Transdermal Drug Delivery System
2007 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

Patch-based transdermal drug delivery offers a convenient way to administer drugs without the drawbacks of standard hypodermic injections relating to issues such as patient acceptability and injection safety. However, conventional transdermal drug delivery is limited to therapeutics where the drug can diffuse across the skin barrier. By using miniaturized needles, a pathway into the human body can be established which allow transport of macromolecular drugs such as insulins or vaccines. These microneedles only penetrate the outermost skin layers, superficial enough not to reach the nerve receptors of the lower skin. Thus, microneedle insertions are perceived as painless.

The thesis presents research in the field of microneedle-based drug delivery with the specific aim of investigating a microneedle-based transdermal patch concept. To enable controllable drug infusion and still maintain an unobtrusive and easy-to-use, patch-like design, the system includes a small active dispenser mechanism. The dispenser is based on a novel thermal actuator consisting of highly expandable microspheres. When actuated, the microspheres expand into a liquid reservoir and, subsequently, dispense stored liquid through outlet holes.

The microneedles are fabricated in monocrystalline silicon by Deep Reactive Ion Etching. The needles are organized in arrays situated on a chip. To allow active delivery, the microneedles are hollow with the needle bore-opening located on the side of the needle. This way, the needle can have a sharp and well-defined needle tip. A sharp needle is a further requirement to achieve microneedle insertion into skin by hand.

The thesis presents fabrication and evaluation of both the microneedle structure and the transdermal patch as such. Issues such as penetration reliability, liquid delivery into the skin and microneedle packaging are discussed. The microneedle patch was also tested and studied in vivo for insulin delivery. Results show that intradermal administration with microneedles give rise to similar insulin concentration as standard subcutaneous delivery with the same dose rate.

Place, publisher, year, edition, pages
Stockholm: KTH, 2007. x, 82 p.
Series
Trita-EE, ISSN 1653-5146 ; 2007:046
Keyword
Microneedle, Transdermal, Intradermal, Drug delivery, DRIE, MEMS, Microsystem
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:kth:diva-4484 (URN)978-91-7178-751-4 (ISBN)
Public defence
2007-09-28, F3, Lindstedsvägen 26, Stockholm, 10:00
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Supervisors
Note
QC 20100623Available from: 2007-09-10 Created: 2007-09-10 Last updated: 2010-06-28Bibliographically approved

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