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Membrane-sealed Hollow Microneedles and Related Administration Schemes for Transdermal Drug Delivery
KTH, School of Electrical Engineering (EES), Microsystem Technology.
KTH, School of Electrical Engineering (EES), Microsystem Technology.ORCID iD: 0000-0001-9552-4234
2008 (English)In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 10, no 2, 271-279 p.Article in journal (Refereed) Published
Abstract [en]

This paper presents fabrication and testing of membrane-sealed hollow microneedles. This novel concept offers the possibility of a sealed microneedle-based transdermal drug delivery system in which the drug is stored and protected from the environment. Sealed microneedles were fabricated by covering the tip openings of out-of-plane silicon microneedles with thin gold membranes. In this way a leak-tight seal was established which hinders both contamination and evaporation. To allow drug release from the microneedles, three different methods of opening the seals were investigated: burst opening by means of pressure; opening by applying a small voltage in the presence of physiological saline; and opening as a result of microneedle insertion into the skin. It was found that a 170 nm thick gold membrane can withstand a pressure of approximately 120 kPa. At higher pressures the membranes burst and the microneedles are opened up. The membranes can also be electrochemically dissolved within 2 min in saline conditions similar to interstitial fluid present in the skin. Moreover, through in vivo tests, it was demonstrated that 170 nm thick membranes break when the microneedles were inserted into skin tissue. The proposed concept was demonstrated as a feasible option for sealing hollow microneedles. This enables the realization of a closed-package transdermal drug delivery system based on microneedles.

Place, publisher, year, edition, pages
2008. Vol. 10, no 2, 271-279 p.
Keyword [en]
National Category
Medical Laboratory and Measurements Technologies
URN: urn:nbn:se:kth:diva-7463DOI: 10.1007/s10544-007-9133-8ISI: 000253525500015ScopusID: 2-s2.0-40349099997OAI: diva2:12494
QC 20100628Available from: 2007-09-10 Created: 2007-09-10 Last updated: 2010-06-28Bibliographically 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.
Trita-EE, ISSN 1653-5146 ; 2007:046
Microneedle, Transdermal, Intradermal, Drug delivery, DRIE, MEMS, Microsystem
National Category
Biomedical Laboratory Science/Technology
urn:nbn:se:kth:diva-4484 (URN)978-91-7178-751-4 (ISBN)
Public defence
2007-09-28, F3, Lindstedsvägen 26, Stockholm, 10:00
QC 20100623Available from: 2007-09-10 Created: 2007-09-10 Last updated: 2010-06-28Bibliographically approved

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