Applications of ultrasonic skin permeation in transdermal drug delivery.
TL;DR: A general review of the transdermal ultrasound drug delivery literature has shown that this technology offers promising potential for non-invasive drug administration, including reported acoustic parameters used for achieving delivery, along with the known intensities and exposure times.
Abstract: Transdermal ultrasound-mediated drug delivery has been studied as a method for needle-less, non-invasive drug administration. Potential obstacles include the stratum corneum, which is not sufficiently passively permeable to allow effective transfer of many medications into the bloodstream without active methods. A general review of the transdermal ultrasound drug delivery literature has shown that this technology offers promising potential for non-invasive drug administration. Included in this review are the reported acoustic parameters used for achieving delivery, along with the known intensities and exposure times. Ultrasound mechanisms are discussed as well as spatial field characteristics. Accurate and precise quantification of the acoustic field used in drug delivery experiments is essential to ensure safety versus efficacy and to avoid potentially harmful bioeffects.
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TL;DR: The skin is refractive to most molecules, especially hydrophilic ones, despite the existence of trans-barrier pathways, and it is essential to maintain this protective barrier even after breaching skin surface for purposes of transdermal drug delivery to cope with cutaneous microbiota.
495 citations
TL;DR: The Bioeffects Committee of the American Institute of Ultrasound in Medicine outlines the wide range of therapeutic ultrasound methods, which are in clinical use or under study, and provides general guidance for ensuring therapeutic ultrasound safety.
Abstract: Applications of ultrasound in medicine for therapeutic purposes have been accepted and beneficial uses of ultrasonic biological effects for many years. Low-power ultrasound of about 1 MHz has been widely applied since the 1950s for physical therapy in conditions such as tendinitis and bursitis. In the 1980s, high-pressure-amplitude shock waves came into use for mechanically resolving kidney stones, and "lithotripsy" rapidly replaced surgery as the most frequent treatment choice. The use of ultrasonic energy for therapy continues to expand, and approved applications now include uterine fibroid ablation, cataract removal (phacoemulsification), surgical tissue cutting and hemostasis, transdermal drug delivery, and bone fracture healing, among others. Undesirable bioeffects can occur, including burns from thermal-based therapies and severe hemorrhage from mechanical-based therapies (eg, lithotripsy). In all of these therapeutic applications of ultrasound bioeffects, standardization, ultrasound dosimetry, benefits assurance, and side-effect risk minimization must be carefully considered to ensure an optimal benefit to risk ratio for the patient. Therapeutic ultrasound typically has well-defined benefits and risks and therefore presents a manageable safety problem to the clinician. However, safety information can be scattered, confusing, or subject to commercial conflicts of interest. Of paramount importance for managing this problem is the communication of practical safety information by authoritative groups, such as the American Institute of Ultrasound in Medicine, to the medical ultrasound community. In this overview, the Bioeffects Committee of the American Institute of Ultrasound in Medicine outlines the wide range of therapeutic ultrasound methods, which are in clinical use or under study, and provides general guidance for ensuring therapeutic ultrasound safety.
495 citations
TL;DR: This is the first paper that highlights the novel and future therapeutic perspectives for the treatment of skin malignancies, new therapeutic agents and promising technological approaches, from nanotechnology to immunotherapy.
244 citations
Cites background from "Applications of ultrasonic skin per..."
...This permeabilizationmethodology may be useful in order to avoid the multiple use of needles [400,406]....
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TL;DR: The underlying principles of HIFU are reviewed and current applications, outcomes, and complications after treatment are presented and recent applications of Focused ultrasound for tumor treatment, drug delivery, vessel occlusion, histotripsy, movement disorders, and vascular, oncologic, and psychiatric applications are reviewed.
Abstract: Ultrasound can penetrate deep into tissues and interact with human tissue via thermal and mechanical mechanisms. The ability to focus an ultrasound beam and its energy onto millimeter-size targets was a significant milestone in the development of therapeutic applications of focused ultrasound. Focused ultrasound can be used as a non-invasive thermal ablation technique for tumor treatment and is being developed as an option to standard oncologic therapies. High-intensity focused ultrasound has now been used for clinical treatment of a variety of solid malignant tumors, including those in the pancreas, liver, kidney, bone, prostate, and breast, as well as uterine fibroids and soft-tissue sarcomas. Magnetic resonance imaging and Ultrasound imaging can be combined with high intensity focused ultrasound to provide real-time imaging during ablation. Magnetic resonance guided focused ultrasound represents a novel non-invasive method of treatment that may play an important role as an alternative to open neurosurgical procedures for treatment of a number of brain disorders. This paper briefly reviews the underlying principles of HIFU and presents current applications, outcomes, and complications after treatment. Recent applications of Focused ultrasound for tumor treatment, drug delivery, vessel occlusion, histotripsy, movement disorders, and vascular, oncologic, and psychiatric applications are reviewed, along with clinical challenges and potential future clinical applications of HIFU.
158 citations
Cites methods from "Applications of ultrasonic skin per..."
...Enhanced skin permeabilization using this technique may replace multiple needle use for medicines such as heparin and insulin or enable diffusion of large molecules (>500 Da) through stratum corneum [114,115]....
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...Enhanced skin permeabilization using this technique may replace multiple needle use for medicines suc as heparin and insulin or enable diffusion of large molecules (>500 Da) through stratum corneum [114,115]....
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References
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Book•
01 Jan 1950
TL;DR: In this article, the authors present a two-dimensional wave equation and simple solutions for the wave equation with respect to the two dimensions of the wave and the two types of vibrations.
Abstract: Fundamentals of Vibration. Transverse Motion: The Vibrating String. Vibrations of Bars. The Two--Dimensional Wave Equation: Vibrations of Membranes and Plates. The Acoustic Wave Equation and Simple Solutions. Reflection and Transmission. Radiation and Reception of Acoustic Waves. Absorption and Attenuation of Sound. Cavities and Waveguides. Pipes, Resonators, and Filters. Noise, Signal Detection, Hearing, and Speech. Architectural Acoustics. Environmental Acoustics. Transduction. Underwater Acoustics. Selected Nonlinear Acoustic Effects. Shock Waves and Explosions. Appendices. Answers to Odd--Numbered Problems. Index.
4,047 citations
TL;DR: In this article, the effectiveness of different forms of nicotine replacement therapy (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes, or a sustained reduction in amount smoked; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker.
Abstract: BACKGROUND: The aim of nicotine replacement therapy (NRT) is to replace nicotine from cigarettes. This reduces withdrawal symptoms associated with smoking cessation thus helping resist the urge to smoke cigarettes. OBJECTIVES: The aims of this review were to determine the effectiveness of the different forms of nicotine replacement therapy (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes, or a sustained reduction in amount smoked; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker; to determine whether combinations of NRT are more effective than one type alone; and to determine its effectiveness compared to other pharmacotherapies. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register in July 2002. SELECTION CRITERIA: Randomized trials in which NRT was compared to placebo or no treatment, or where different doses of NRT were compared. We excluded trials which did not report cessation rates, and those with follow-up of less than six months. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of subjects, the dose and duration and form of nicotine therapy, the outcome measures, method of randomization, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed effects model (Peto). MAIN RESULTS: We identified 110 trials; 96 with a non NRT control group. The odds ratio for abstinence with NRT compared to control was 1.74 (95% confidence interval 1.64 - 1.86), The odds ratios for the different forms of NRT were 1.66 for gum, 1.74 for patches, 2.27 for nasal spray, 2.08 for inhaled nicotine and 2.08 for nicotine sublingual tablet/lozenge. These odds were largely independent of the duration of therapy, the intensity of additional support provided or the setting in which the NRT was offered. In highly dependent smokers there was a significant benefit of 4 mg gum compared with 2mg gum (odds ratio 2.67, 95% confidence interval 1.69 - 4.22). There was weak evidence that combinations of forms of NRT are more effective. Higher doses of nicotine patch may produce small increases in quit rates. Only one study directly compared NRT to another pharmacotherapy, in which bupropion was significantly more effective than nicotine patch or placebo. REVIEWER'S CONCLUSIONS: All of the commercially available forms of NRT (nicotine gum, transdermal patch, the nicotine nasal spray, nicotine inhaler and nicotine sublingual tablets/lozenges) are effective as part of a strategy to promote smoking cessation. They increase quit rates approximately 1.5 to 2 fold regardless of setting. The effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the smoker. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT. There is promising evidence that bupropion may be more effective than NRT (either alone or in combination). However, its most appropriate place in the therapeutic armamentarium requires further study and consideration.
2,173 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
"Applications of ultrasonic skin per..." refers background or methods in this paper
...Readers are also directed to several recent, comprehensive publications for further commentary on transdermal drug delivery, including ultrasound-based methods [3,4,6,14] ....
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...Ultrasound is one of several needle-less methods currently under investigation or on the market [4-6] ....
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...This technology has the potential to be either as successful as the nicotine patch [4,64] or fall by the wayside like EXUBERA ® [57] ....
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TL;DR: Evidence for benefit from nicotine replacement therapy in hospital patients is inconclusive, although the results of a trial reported in this issue of Thorax give cause for optimism and should stimulate further studies.
Abstract: Evidence for benefit from nicotine replacement therapy in hospital patients is inconclusive, although the results of a trial reported in this issue of Thorax give cause for optimism and should stimulate further studies.
Most smokers become nicotine dependent and, when they stop smoking, experience withdrawal symptoms and craving. Nicotine replacement therapy (NRT) reduces these unpleasant symptoms and, theoretically, should decrease the risk of relapse. Smoking cessation is properly defined as validated sustained abstinence from cigarettes and/or other tobacco products for at least 6 months, but preferably for 1 year. This editorial includes evidence only from those studies which have applied such a definition and which have specified their settings and populations.
NRT is available as chewing gum, transdermal patches, sublingual tablets, lozenges, inhalation cartridges and nasal spray. In specialised cessation clinics1–8 and in primary care,9,10 prospective randomised clinical trials have shown that NRT, used as an adjunct to advice and support, results in better cessation rates than does advice and support alone. In the clinics success rates with NRT tend to be higher (11–30%) and more consistent than in primary care, where some studies have found no significant difference from placebo.11–14 One study in primary care showed 8% success with nicotine chewing gum compared with 4% with advice plus leaflet, but there was no placebo controlled arm.15 Two studies of transdermal nicotine in primary care have shown success rates of around 10%, which were superior to those with placebo (around 6%).9,10 The benefit for transdermal nicotine in cessation clinics6–8 and in primary care9,10 is thus clear, whereas nicotine chewing gum,1–5 inhaler,16,17 …
1,097 citations
"Applications of ultrasonic skin per..." refers methods in this paper
...This technology has the potential to be either as successful as the nicotine patch [4,64] or fall by the wayside like EXUBERA ® [57] ....
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TL;DR: Low-frequency ultrasound was shown to increase the permeability of human skin to many drugs, including high molecular weight proteins, by several orders of magnitude, thus making transdermal administration of these molecules potentially feasible.
Abstract: Transdermal drug delivery offers a potential method of drug administration. However, its application has been limited to a few low molecular weight compounds because of the extremely low permeability of human skin. Low-frequency ultrasound was shown to increase the permeability of human skin to many drugs, including high molecular weight proteins, by several orders of magnitude, thus making transdermal administration of these molecules potentially feasible. It was possible to deliver and control therapeutic doses of proteins such as insulin, interferon gamma, and erythropoeitin across human skin. Low-frequency ultrasound is thus a potential noninvasive substitute for traditional methods of drug delivery, such as injections.
803 citations
"Applications of ultrasonic skin per..." refers background in this paper
...Insofar as ultrasound is known to increase transdermal protein delivery [58] , the mechanisms of this enhanced transport have not yet been fully characterized....
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