Microneedle technologies for (trans)dermal drug and vaccine delivery.
TL;DR: This review describes different production methods for solid and hollow microneedles as well as conditions that influence skin penetration and the view on research and development that is needed to rendermicroneedle-based (trans)dermal drug delivery technologies clinically useful in the near future.
About: This article is published in Journal of Controlled Release.The article was published on 2012-07-20. It has received 499 citations till now. The article focuses on the topics: Drug delivery.
Citations
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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
TL;DR: This review outlines recent developments in the controlled delivery of insulin, including oral, nasal, pulmonary, transdermal, subcutaneous and closed-loop insulin delivery.
Abstract: Insulin is essential for type 1 and advanced type 2 diabetics to maintain blood glucose levels and prolong lives. The traditional administration requires frequent subcutaneous insulin injections that are associated with poor patient compliance, including pain, local tissue necrosis, infection, and nerve damage. Taking advantage of emerging micro- and nanotechnologies, numerous alternative strategies integrated with chemical approaches for insulin delivery have been investigated. This review outlines recent developments in the controlled delivery of insulin, including oral, nasal, pulmonary, transdermal, subcutaneous and closed-loop insulin delivery. Perspectives from new materials, formulations and devices at the micro- or nano-scales are specifically surveyed. Advantages and limitations of current delivery methods, as well as future opportunities and challenges are also discussed.
347 citations
TL;DR: In this review, different types of microneedles are described and their methods of fabrication highlighted and concerns and challenges regardingmicroneedle use are discussed.
Abstract: Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use.
312 citations
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01 Jan 2010
TL;DR: This exam consists of 50 questions and you must select the one best response that is the best response to receive credit for each question.
Abstract: Instructions This exam consists of 50 questions. You may write on the exam itself, but be sure to answer all your questions on a “Scantron” sheet with a #2 pencil. For each question there is one response that is the best response. You must select the one best response to receive credit for each question. If you select more than one response for a question, then you will receive no credit for that question.
306 citations
TL;DR: A concerted effort has been made within this review to highlight the current advances of microneedles, and to provide an update of pharmaceutical research in the field ofmicroneedle-assisted transdermal drug delivery systems.
288 citations
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
"Microneedle technologies for (trans..." refers background or methods in this paper
...driven fluid flow, thereby allowing faster rates of drug delivery [10, 14, 27, 28]....
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...Therefore, several methods have been developed for (trans)dermal drug delivery, such as chemical and lipid enhancers, and electric fields for iontophoresis [6, 14-17]....
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...the microneedles are removed and a patch containing the drug formulation is applied onto the site of microneedle application so that the drug can diffuse through the formed microchannels into the skin [14, 27, 28, 43]....
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TL;DR: Protein antigens presented in a highly arrayed structure, such as might be found in large nondenatured aggregate species, are highly potent in inducing antibody responses even in the absence of T-cell help.
Abstract: The capacity of protein aggregates to enhance immune responses to the monomeric form of the protein has been known for over a half-century. Despite the clear connection between protein aggregates and antibody mediated adverse events in treatment with early therapeutic protein products such as intravenous immune globulin (IVIG) and human growth hormone, surprisingly little is known about the nature of the aggregate species responsible for such effects. This review focuses on a framework for understanding how aggregate species potentially interact with the immune system to enhance immune responses, garnered from basic immunologic research. Thus, protein antigens presented in a highly arrayed structure, such as might be found in large nondenatured aggregate species, are highly potent in inducing antibody responses even in the absence of T-cell help. Their potency may relate to the ability of multivalent protein species to extensively cross-link B-cell receptor, which (1) activates B cells via Bt kinases to proliferate, and (2) targets protein to class II major histocompatability complex (MHC)-loading compartments, efficiently eliciting T-cell help for antibody responses. The review further focuses on protein aggregates as they affect an immunogenicity risk assessment, the use of animal models and studies in uncovering effects of protein aggregates, and changes in product manufacture and packaging that may affect generation of protein aggregates.
1,287 citations
"Microneedle technologies for (trans..." refers background in this paper
...important risk factors for unwanted protein immunogenicity [145, 151, 152]....
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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
TL;DR: This review identifies diseases that are most in need of new health technologies, special design criteria for LOC devices to be deployed in a variety of resource-poor settings, and review past research into LOC devices for global health.
Abstract: A rapidly emerging field in lab-on-a-chip (LOC) research is the development of devices to improve the health of people in developing countries. In this review, we identify diseases that are most in need of new health technologies, discuss special design criteria for LOC devices to be deployed in a variety of resource-poor settings, and review past research into LOC devices for global health. We focus mainly on diagnostics, the nearest-term application in this field.
840 citations
"Microneedle technologies for (trans..." refers background in this paper
...the delivery of insulin accordingly [1-3, 21, 22, 42, 155]....
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...The ultimate goal of “lab-on-a-chip” approaches is to create minimally-invasive, fully automated modules for constantly extracting and analyzing biological fluid and directly responding on the analytical results by the delivery of drugs [1-5]....
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