Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies
25 Nov 2003-Proceedings of the National Academy of Sciences of the United States of America (National Academy of Sciences)-Vol. 100, Iss: 24, pp 13755-13760
TL;DR: Microfabrication techniques for silicon, metal, and biodegradable polymer microneedle arrays having solid and hollow bores with tapered and beveled tips and feature sizes from 1 to 1,000 μm allowed flow of microliter quantities into skin in vivo, including microinjection of insulin to reduce blood glucose levels in diabetic rats.
Abstract: Arrays of micrometer-scale needles could be used to deliver drugs, proteins, and particles across skin in a minimally invasive manner. We therefore developed microfabrication techniques for silicon, metal, and biodegradable polymer microneedle arrays having solid and hollow bores with tapered and beveled tips and feature sizes from 1 to 1,000 μm. When solid microneedles were used, skin permeability was increased in vitro by orders of magnitude for macromolecules and particles up to 50 nm in radius. Intracellular delivery of molecules into viable cells was also achieved with high efficiency. Hollow microneedles permitted flow of microliter quantities into skin in vivo, including microinjection of insulin to reduce blood glucose levels in diabetic rats.
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TL;DR: Microneedles represent a promising technology to deliver therapeutic compounds into the skin for a range of possible applications and the ratio of microneedle fracture force to skin insertion force was found to be optimal for needles with small tip radius and large wall thickness.
1,298 citations
TL;DR: The already significant impact this field has made on the administration of various pharmaceuticals is discussed; limitations of the current technology are explored; methods under exploration for overcoming these limitations and the challenges ahead are discussed.
Abstract: The past twenty five years have seen an explosion in the creation and discovery of new medicinal agents. Related innovations in drug delivery systems have not only enabled the successful implementation of many of these novel pharmaceuticals, but have also permitted the development of new medical treatments with existing drugs. The creation of transdermal delivery systems has been one of the most important of these innovations, offering a number of advantages over the oral route. In this article, we discuss the already significant impact this field has made on the administration of various pharmaceuticals; explore limitations of the current technology; and discuss methods under exploration for overcoming these limitations and the challenges ahead.
1,275 citations
Cites background from "Microfabricated needles for transde..."
...In vitro experiments have shown that inserting MICRONEEDLES into skin can increase permeability by orders of magnitude for small drugs, large macromolecules and nanoparticle...
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TL;DR: Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications.
1,271 citations
Cites background from "Microfabricated needles for transde..."
...The first studies of biotherapeutic delivery using microneedles employed silicon or glass microneedles for insulin delivery [38, 142], which demonstrated drops in blood-glucose levels after microneedle injection....
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...Similarly, microneedle arrays have been pressed into a monolayer of prostate cancer cells bathed in a solution of calcein, a small fluorescent marker compound [38]....
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TL;DR: Results indicate that biodegradable polymer microneedles can be fabricated with an appropriate geometry and sufficient strength to insert into skin, and thereby dramatically increase transdermal transport of molecules.
827 citations
TL;DR: It is concluded that dissolving microneedles can be designed to gently encapsulate molecules, insert into skin, and enable bolus or sustained release delivery and leave behind no biohazardous sharp medical waste.
743 citations
Cites background from "Microfabricated needles for transde..."
...Previous studies have also pretreated skin by piercing it with microneedles and then applying a topical formulation or patch to deliver drug through the permeabilized skin [6,25]....
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...One approach involves pretreatment of skin with microneedles, followed by application of a transdermal patch for extended drug delivery through the permeabilized skin [6]....
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01 Jan 1997TL;DR: The second edition of the Fundamentals of Microfabrication as discussed by the authors provides an in-depth coverage of the science of miniaturization, its methods, and materials, from the fundamentals of lithography through bonding and packaging to quantum structures and molecular engineering.
Abstract: MEMS technology and applications have grown at a tremendous pace, while structural dimensions have grown smaller and smaller, reaching down even to the molecular level. With this movement have come new types of applications and rapid advances in the technologies and techniques needed to fabricate the increasingly miniature devices that are literally changing our world.A bestseller in its first edition, Fundamentals of Microfabrication, Second Edition reflects the many developments in methods, materials, and applications that have emerged recently. Renowned author Marc Madou has added exercise sets to each chapter, thus answering the need for a textbook in this field.Fundamentals of Microfabrication, Second Edition offers unique, in-depth coverage of the science of miniaturization, its methods, and materials. From the fundamentals of lithography through bonding and packaging to quantum structures and molecular engineering, it provides the background, tools, and directions you need to confidently choose fabrication methods and materials for a particular miniaturization problem.New in the Second EditionRevised chapters that reflect the many recent advances in the fieldUpdated and enhanced discussions of topics including DNA arrays, microfluidics, micromolding techniques, and nanotechnology In-depth coverage of bio-MEMs, RF-MEMs, high-temperature, and optical MEMs.Many more links to the WebProblem sets in each chapter
2,334 citations
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01 Jan 1968
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