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Book ChapterDOI

Sonophoresis: Ultrasound-Mediated Transdermal Drug Delivery

01 Jan 2017-pp 3-14
TL;DR: This chapter provides an overview of the historical perspective, mechanisms, and applications of low-frequency ultrasound, which has been shown to enhance skin permeability to various small and large molecules including proteins.
Abstract: Transdermal drug delivery offers a patient-compliant mode of drug administration. Its applications, however, are limited to low-molecular-weight hydrophobic drugs. Application of ultrasound has been shown to enhance transdermal transport of drugs, a phenomenon known as sonophoresis. Ultrasound under various conditions has been used to perform sonophoresis. The use of low-frequency ultrasound (f < 100 kHz) is particularly effective in enhancing skin permeability. Low-frequency sonophoresis has been shown to enhance skin permeability to various small and large molecules including proteins. A device based on low-frequency ultrasound has also been approved for human use. This chapter provides an overview of the historical perspective, mechanisms, and applications of low-frequency ultrasound.
Citations
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Journal ArticleDOI
TL;DR: This review discusses the application of high intensity focus ultrasound for non-invasive tumor ablation and immunomodulatory effects of ultrasound, as well as the efficacy of nanoparticle-enhanced ultrasound therapies for different medical conditions.
Abstract: While ultrasound is most widely known for its use in diagnostic imaging, the energy carried by ultrasound waves can be utilized to influence cell function and drug delivery. Consequently, our ability to use ultrasound energy at a given intensity unlocks the opportunity to use the ultrasound for therapeutic applications. Indeed, in the last decade ultrasound-based therapies have emerged with promising treatment modalities for several medical conditions. More recently, ultrasound in combination with nanomedicines, i.e., nanoparticles, has been shown to have substantial potential to enhance the efficacy of many treatments including cancer, Alzheimer disease or osteoarthritis. The concept of ultrasound combined with drug delivery is still in its infancy and more research is needed to unfold the mechanisms and interactions of ultrasound with different nanoparticles types and with various cell types. Here we present the state-of-art in ultrasound and ultrasound-assisted drug delivery with a particular focus on cancer treatments. Notably, this review discusses the application of high intensity focus ultrasound for non-invasive tumor ablation and immunomodulatory effects of ultrasound, as well as the efficacy of nanoparticle-enhanced ultrasound therapies for different medical conditions. Furthermore, this review presents safety considerations related to ultrasound technology and gives recommendations in the context of system design and operation.

110 citations

Journal ArticleDOI
TL;DR: This review describes combined use of frequently used nanocarriers with the most efficient physical methods (microneedles, iontophoresis, ultrasound and electroporation) and demonstrates superiority of the combined use and physical methods in drug penetration enhancement compared to their single use.

69 citations

Journal ArticleDOI
TL;DR: In this paper, the skin structure and major obstacle for transdermal drug delivery, different nanocarriers, i.e., nanoparticles, ethosomes, dendrimers, liposomes, etc., have been discussed.
Abstract: The transdermal route of administration provides numerous advantages over conventional routes i.e., oral or injectable for the treatment of different diseases and cosmetics applications. The skin also works as a reservoir, thus deliver the penetrated drug for more extended periods in a sustained manner. It reduces toxicity and local irritation due to multiple sites for absorption and owes the option of avoiding systemic side effects. However, the transdermal route of delivery for many drugs is limited since very few drugs can be delivered at a viable rate using this route. The stratum corneum of skin works as an effective barrier, limiting most drugs' penetration posing difficulty to cross through the skin. Fortunately, some non-invasive methods can significantly enhance the penetration of drugs through this barrier. The use of nanocarriers for increasing the range of available drugs for the transdermal delivery has emerged as a valuable and exciting alternative. Both the lipophilic and hydrophilic drugs can be delivered via a range of nanocarriers through the stratum corneum with the possibility of having local or systemic effects to treat various diseases. In this review, the skin structure and major obstacle for transdermal drug delivery, different nanocarriers used for transdermal delivery, i.e., nanoparticles, ethosomes, dendrimers, liposomes, etc., have been discussed. Some recent examples of the combination of nanocarrier and physical methods, including iontophoresis, ultrasound, laser, and microneedles, have also been discussed for improving the therapeutic efficacy of transdermal drugs. Limitations and future perspectives of nanocarriers for transdermal drug delivery have been summarized at the end of this manuscript.

64 citations

Journal ArticleDOI
TL;DR: Various approaches towards the stimulation of drug penetration through and into the stratum corneum and hair follicles, which are considered to be promising for the future improvement of superficial antifungal therapy as providing the drug localization and prolonged storage property at the targeted area are summarized.
Abstract: Topical therapy of superficial fungal infections allows the prevention of systemic side effects and provides drug targeting at the site of disease. However, an appropriate drug concentration in these sites should be provided to ensure the efficacy of such local treatment. The enhancement of intra- and transdermal penetration and accumulation of antifungal drugs is an important aspect here. The present overview is focused on novel nano-based formulations served to improve antimycotic penetration through the skin. Furthermore, it summarizes various approaches towards the stimulation of drug penetration through and into the stratum corneum and hair follicles, which are considered to be promising for the future improvement of superficial antifungal therapy as providing the drug localization and prolonged storage property at the targeted area.

13 citations

Journal ArticleDOI
TL;DR: Conclusively, sonophoresis with the proposed cavitation seed demonstrated the significant improvement in TDD and the possibility of macromolecule delivery into the skin.
Abstract: The sonophoresis, which utilizes ultrasound for transdermal drug delivery (TDD), can improve the efficiency of drug delivery for a variety of drugs predominantly due to cavitation effect. In order to increase the efficacy of sonophoresis, we propose an alternative cavitation seed specialized for sonophoresis, which can be concentrated on the skin surface by gravity adapting perfluorohexane as core. Methods: in vitro and in vivo experiments were conducted to assess the effect of the specialized cavitation seed. High-performance liquid chromatography (HPLC) was used for in vitro experiments on porcine skin with ferulic acid, and an optical imaging system was used for in vivo experiments on the rat model with fluorescein isothiocyanate-dextran (FD, 150 kDa), respectively. Results: The amount of ferulic acid delivered by sonophoresis with the proposed cavitation seed was approximately 1700 times greater than the amount delivered by diffusion. FD could be delivered to a depth of $500~\mu \text{m}$ under the skin, and the average total flux in the region of interest was increased 6.4-fold for the group using sonophoresis with the cavitation seed compared to the group using diffusion. Conclusion: Conclusively, sonophoresis with the proposed cavitation seed demonstrated the significant improvement in TDD and the possibility of macromolecule delivery into the skin. Significance: This approach has potential to be a main TDD method for variety of applications including medicine and cosmetics.

12 citations


Cites background from "Sonophoresis: Ultrasound-Mediated T..."

  • ...In addition, a shock wave can be induced by the rapid formation of a gas pocket so that the SC near the vaporization point can be disturbed [39]....

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References
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Journal ArticleDOI
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

Journal ArticleDOI
TL;DR: In this paper, a numerical method was proposed to solve the problem of balloon bubble collapse near a plane solid wall, using finite time steps and an iterative technique for applying the boundary conditions at infinity directly to the liquid at a finite distance from the free surface.
Abstract: Vapor bubble collapse problems lacking spherical symmetry are solved here using a numerical method designed especially for these problems. Viscosity and compressibility in the liquid are neglected. The method uses finite time steps and features an iterative technique for applying the boundary conditions at infinity directly to the liquid at a finite distance from the free surface. Two specific cases of initially spherical bubbles collapsing near a plane solid wall were simulated: a bubble initially in contact with the wall, and a bubble initially half its radius from the wall at the closest point. It is shown that the bubble develops a jet directed towards the wall rather early in the collapse history. Free surface shapes and velocities are presented at various stages in the collapse. Velocities are scaled like (Δp/ρ)^1/2 where ρ is the density of the liquid and Δp is the constant difference between the ambient liquid pressure and the pressure in the cavity. For Δp/ρ = 10^6 (cm/sec)^2 ~ 1 atm./density of water the jet had a speed of about 130 m/sec in the first case and 170 m/sec in the second when it struck the opposite side of the bubble. Such jet velocities are of a magnitude which can explain cavitation damage. The jet develops so early in the bubble collapse history that compressibility effects in the liquid and the vapor are not important.

890 citations

Journal ArticleDOI
TL;DR: Ultrasound, which is routinely used for diagnostic imaging applications, is now being adopted in various drug delivery and other therapeutic applications, and the principles and current status are reviewed.
Abstract: Ultrasound, which is routinely used for diagnostic imaging applications, is now being adopted in various drug delivery and other therapeutic applications. Ultrasound has been shown to facilitate the delivery of drugs across the skin, promote gene therapy to targeted tissues, deliver chemotherapeutic drugs into tumours and deliver thrombolytic drugs into blood clots. In addition, ultrasound has also been shown to facilitate the healing of wounds and bone fractures. This article reviews the principles and current status of ultrasound-based treatments.

813 citations

Journal ArticleDOI
11 Aug 1995-Science
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

Journal ArticleDOI
TL;DR: In this paper, the dynamics of the bubbles in the neighbourhood of a solid boundary were studied by means of high-speed photography using a rotating-mirror camera with framing rates of up to 300000 frame/s.
Abstract: Cavitation bubbles were produced by focusing giant pulses of a Q-switched ruby laser into distilled water. The dynamics of the bubbles in the neighbourhood of a solid boundary were studied by means of high-speed photography using a rotating-mirror camera with framing rates of up to 300000 frame/s. Bubble motion was evaluated from the frames with the aid of a digital computer using a graphical input device. Smoothed distance-time curves of different portions of the bubble wall were obtained also, allowing a reliable calculation of bubble-wall velocities (except at the actual instant of collapse). One of the numerical examples of the collapse of a spherical bubble near a plane solid boundary obtained by Plesset & Chapman could be realized experimentally. A comparison of the bubble shapes shows good agreement.

672 citations