Microneedles for drug and vaccine delivery.
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.
About: This article is published in Advanced Drug Delivery Reviews.The article was published on 2012-11-01 and is currently open access. It has received 1271 citations till now.
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TL;DR: This Review summarizes the recent progress of flexible sensing electronics for their use in wearable/attachable health monitoring systems, and presents an overview of different materials and configurations for flexible sensors, including piezo-resistive, piezos-electrical, capacitive, and field effect transistor based devices.
Abstract: Wearable or attachable health monitoring smart systems are considered to be the next generation of personal portable devices for remote medicine practices. Smart flexible sensing electronics are components crucial in endowing health monitoring systems with the capability of real-time tracking of physiological signals. These signals are closely associated with body conditions, such as heart rate, wrist pulse, body temperature, blood/intraocular pressure and blood/sweat bio-information. Monitoring such physiological signals provides a convenient and non-invasive way for disease diagnoses and health assessments. This Review summarizes the recent progress of flexible sensing electronics for their use in wearable/attachable health monitoring systems. Meanwhile, we present an overview of different materials and configurations for flexible sensors, including piezo-resistive, piezo-electrical, capacitive, and field effect transistor based devices, and analyze the working principles in monitoring physiological signals. In addition, the future perspectives of wearable healthcare systems and the technical demands on their commercialization are briefly discussed.
708 citations
TL;DR: The progress and current status of the transdermal drug delivery field is detailed, numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems are described and particular attention is paid to the emerging field of microneedle technologies.
Abstract: The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies.
570 citations
Cites background or methods from "Microneedles for drug and vaccine d..."
...Generally, there are four strategies of TDD using MN (Figure 15) [22,123]....
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...enhancing flux of the molecules ranging from small hydrophilic molecules such as alendronate [52] to macromolecules, including low molecular weight heparins [4,121], insulin [122] and vaccines [123], in a pain-free manner [112,124]....
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TL;DR: A new form of delivery system called the microneedles helps to enhance the delivery of the drug through this route and overcoming the various problems associated with the conventional formulations.
548 citations
TL;DR: In this paper, a review of microneedle arrays can increase the number of compounds amenable to transdermal delivery by penetrating the skin's protective barrier, the stratum corneum, and creating a pathway for drug permeation to the dermal tissue below.
Abstract: Transdermal drug delivery offers a number of advantages for the patient, due not only its non-invasive and convenient nature, but also factors such as avoidance of first pass metabolism and prevention of gastrointestinal degradation. It has been demonstrated that microneedle arrays can increase the number of compounds amenable to transdermal delivery by penetrating the skin's protective barrier, the stratum corneum , and creating a pathway for drug permeation to the dermal tissue below. Microneedles have been extensively investigated in recent decades for drug and vaccine delivery as well as minimally invasive patient monitoring/diagnosis. This review focuses on a range of critically important aspects of microneedle technology, namely their material composition, manufacturing techniques, methods of evaluation and commercial translation to the clinic for patient benefit and economic return. Microneedle research and development is finally now at the stage where commercialisation is a realistic possibility. However, progress is still required in the areas of scaled-up manufacture and regulatory approval.
525 citations
TL;DR: The pathophysiology of chronic wounds is discussed and then the materials used for engineering drug delivery systems are discussed, and the architecture of the delivery platform and its ability to modulate drug delivery are discussed.
440 citations
Cites background from "Microneedles for drug and vaccine d..."
...These microneedles can be categorized into four groups (Figure 6a): i) solid microneedles disrupting the epidermis barrier and enabling the penetration of topically administered drugs [202], ii) microneedles coated with drugs that can penetrate the tissue and deliver their payload in there [203], iii) dissolvable microneedles that penetrate the tissue and stay there and release their payload gradually as they degrade (Figure 6b) [204– 206], and iv) hollow microneedles that penetrate the tissue and facilitate the active delivery of drugs into the region of interest [207]....
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References
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TL;DR: Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound for delivery of macromolecules and vaccines.
Abstract: Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase its impact on medicine.
2,595 citations
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
"Microneedles for drug and vaccine d..." refers background in this paper
...This article reviews this body of work, building upon previous review articles in the field [10,14–33]....
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TL;DR: These microneedle arrays could be easily inserted into skin without breaking and were shown to increase permeability of human skin in vitro to a model drug, calcein, by up to 4 orders of magnitude.
1,181 citations
"Microneedles for drug and vaccine d..." refers background or methods in this paper
...Short silicon microneedles have been prepared using a silicon dryetching process based on reactive ion etching with a chromium mask [40, 53], as well as isotropic etching in an inductively coupled plasma etcher [54]....
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...This group produced the first journal article on drug delivery using microneedles [40] and has continued to perform microneedles research since then....
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..., thereby partially plugging the pores) and was shown to increase by more than 10,000-fold when microneedles were inserted and immediately removed [40]....
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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: 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.
795 citations
"Microneedles for drug and vaccine d..." refers background in this paper
...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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