The Experts below are selected from a list of 1065 Experts worldwide ranked by ideXlab platform

Samir Mitragotri - One of the best experts on this subject based on the ideXlab platform.

  • Sonophoresis ultrasound mediated transdermal drug delivery
    2017
    Co-Authors: Samir Mitragotri
    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.

  • Low-frequency Sonophoresis: current status and future prospects
    Adv Drug Deliv Rev, 2008
    Co-Authors: Makoto Ogura, Sumit Paliwal, Samir Mitragotri
    Abstract:

    Application of ultrasound enhances skin permeability to drugs, a phenomenon referred to as Sonophoresis. Significant strides have been made in Sonophoresis research in recent years, especially under low-frequency conditions (20 kHz

  • Low-frequency Sonophoresis: ultrastructural basis for stratum corneum permeability assessed using quantum dots.
    The Journal of investigative dermatology, 2006
    Co-Authors: Sumit Paliwal, Gopinathan K. Menon, Samir Mitragotri
    Abstract:

    Low-frequency Sonophoresis (LFS) has been well documented to enhance the permeability of skin to macromolecular drugs via induction of localized transport regions. However, the organizational details of epidermis, specifically stratum corneum (SC), during Sonophoresis are beyond the resolution limit of common histo-optical microscopy tools, which fail to reveal any notable structural alterations in these regions at a submicroscopic scale. Here we report, using quantum dots (QDs) as a tracer and confocal microscopy and transmission electron microscopy (TEM) (with OsO(4) and RuO(4) post-fixation) as visualization methods, on LFS-induced permeation pathways in the SC. QDs (20 nm diameter) penetrated well beyond the SC. TEM revealed that ultrasound significantly increased the frequency of occurrence of the otherwise scattered and separated lacunar spaces in the SC. A significant increase in lacunar dimensions was observed when 1% w/v sodium lauryl sulfate was added to the coupling medium. These studies show that LFS induces dilatation and higher connectivity of voids in the SC, possibly leading to formation of a three-dimensional porous network, which is capable of transporting QDs as well as macromolecules across the SC. This contention is consistent with previously conceived theoretical mechanistic understanding of LFS-induced enhanced transport across the skin.

  • low frequency Sonophoresis a review
    Advanced Drug Delivery Reviews, 2004
    Co-Authors: Samir Mitragotri, Joseph Kost
    Abstract:

    Application of ultrasound enhances skin permeability to a variety of molecules (Sonophoresis). The enhancement induced by ultrasound is particularly significant at low-frequencies (f<100 kHz, low-frequency Sonophoresis). This review summarizes mechanisms and applications of low-frequency Sonophoresis. In vitro, in vivo, as well as clinical studies demonstrating the effect of low-frequency ultrasound on transdermal drug delivery and glucose extraction are summarized. Mechanistic insights gained through a number of investigations are also reviewed. Finally, reports on the synergistic effect of low-frequency ultrasound with other enhancers including chemicals and iontophoresis are summarized.

  • Low-frequency Sonophoresis: A review
    Advanced Drug Delivery Reviews, 2004
    Co-Authors: Samir Mitragotri, Joseph Kost
    Abstract:

    Application of ultrasound enhances skin permeability to a variety of molecules (Sonophoresis). The enhancement induced by ultrasound is particularly significant at low-frequencies (f

Robert Langer - One of the best experts on this subject based on the ideXlab platform.

  • ultrasound mediated transdermal drug delivery mechanisms scope and emerging trends
    Journal of Controlled Release, 2011
    Co-Authors: Baris E. Polat, Robert Langer, Douglas P Hart, Daniel Blankschtein
    Abstract:

    The use of ultrasound for the delivery of drugs to, or through, the skin is commonly known as Sonophoresis or phonophoresis. The use of therapeutic and high frequencies of ultrasound (≥ 0.7 MHz) for Sonophoresis (HFS) dates back to as early as the 1950s, while low-frequency Sonophoresis (LFS, 20 – 100 kHz) has only been investigated significantly during the past two decades. Although HFS and LFS are similar because they both utilize ultrasound to increase the skin penetration of permeants, the mechanisms associated with each physical enhancer are different. Specifically, the location of cavitation and the extent to which each process can increase skin permeability are quite dissimilar. Although the applications of both technologies are different, they each have strengths that could allow them to improve current methods of local, regional, and systemic drug delivery. In this review, we will discuss the mechanisms associated with both HFS and LFS, specifically concentrating on the key mechanistic differences between these two skin treatment methods. Background on the relevant physics associated with ultrasound transmitted through aqueous media will also be discussed, along with implications of these phenomena on Sonophoresis. Finally, a thorough review of the literature is included, dating back to the first published reports of Sonophoresis, including a discussion of emerging trends in the field.

  • Ultrasound-mediated transdermal drug delivery: Mechanisms, scope, and emerging trends
    Journal of Controlled Release, 2011
    Co-Authors: Baris E. Polat, Douglas Hart, Robert Langer, Daniel Blankschtein
    Abstract:

    The use of ultrasound for the delivery of drugs to, or through, the skin is commonly known as Sonophoresis or phonophoresis. The use of therapeutic and high frequencies of ultrasound (???0.7 MHz) for Sonophoresis (HFS) dates back to as early as the 1950s, while low-frequency Sonophoresis (LFS, 20-100 kHz) has only been investigated significantly during the past two decades. Although HFS and LFS are similar because they both utilize ultrasound to increase the skin penetration of permeants, the mechanisms associated with each physical enhancer are different. Specifically, the location of cavitation and the extent to which each process can increase skin permeability are quite dissimilar. Although the applications of both technologies are different, they each have strengths that could allow them to improve current methods of local, regional, and systemic drug delivery. In this review, we will discuss the mechanisms associated with both HFS and LFS, specifically concentrating on the key mechanistic differences between these two skin treatment methods. Background on the relevant physics associated with ultrasound transmitted through aqueous media will also be discussed, along with implications of these phenomena on Sonophoresis. Finally, a thorough review of the literature is included, dating back to the first published reports of Sonophoresis, including a discussion of emerging trends in the field. ?? 2011 Elsevier B.V.

  • dependence of low frequency Sonophoresis on ultrasound parameters distance of the horn and intensity
    International Journal of Pharmaceutics, 2002
    Co-Authors: Takaaki Terahara, Joseph Kost, Samir Mitragotri, Robert Langer
    Abstract:

    Abstract Sonophoresis at a frequency of 20 kHz has been shown to enhance transdermal drug delivery, a phenomenon referred to as low-frequency Sonophoresis. This study provides an investigation of the dependence of low-frequency Sonophoresis on various ultrasound parameters, including the distance of the horn from the skin, intensity, and frequency. We performed in vitro experiments with full thickness pig skin to measure enhancements of skin conductivity and drug permeability. Ultrasound was applied to pretreat the skin using a sonicator operating at a frequency of either 20 or 40 kHz. We also measured pitting of aluminum foil to measure cavitation, which is the principal mechanism of low-frequency Sonophoresis. The skin conductivity enhancement was found to be inversely proportional to the distance of the horn from the skin. As the intensity increased, skin conductivity enhancement also increased up to a certain threshold, and then dropped off. The intensities (Imax) at which maximum enhancement occur are about 14 W/cm2 for 20 kHz and 17 W/cm2 for 40 kHz. These findings may be useful in optimizing low-frequency Sonophoresis. Overall, the dependence of transport on ultrasound parameters is similar to that of aluminum foil pitting. These results support the role of cavitation in low-frequency Sonophoresis.

  • porous resins as a cavitation enhancer for low frequency Sonophoresis
    Journal of Pharmaceutical Sciences, 2002
    Co-Authors: Takaaki Terahara, Samir Mitragotri, Robert Langer
    Abstract:

    Abstract The application of low‐frequency ultrasound enhances drug transport through the skin, a phenomenon referred to as low‐frequency Sonophoresis. This enhancement is mediated through cavitation, the formation and collapse of gaseous bubbles. We hypothesized that the efficacy of low‐frequency Sonophoresis can be significantly enhanced by provision of nuclei for cavitation. In this study, we used two porous resins, Diaion® HP20 and Diaion HP2MG (2MG), as cavitation nuclei. We measured the effect of these resins on cavitation using pitting of aluminum foil. 2MG showed a higher efficacy in enhancing cavitation compared with Diaion HP20. 2MG was also effective in enhancing transdermal mannitol transport. These results confirm that the addition of cavitation nuclei such as porous resins further increases the effect of low‐frequency ultrasound on skin permeability. © 2002 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:753–759, 2002

  • Porous resins as a cavitation enhancer for low-frequency Sonophoresis
    Journal of Pharmaceutical Sciences, 2002
    Co-Authors: Takafumi Terahara, Samir Mitragotri, Robert Langer
    Abstract:

    The application of low-frequency ultrasound enhances drug transport through the skin, a phenomenon referred to as low-frequency Sonophoresis. This enhancement is mediated through cavitation, the formation and collapse of gaseous bubbles. We hypothesized that the efficacy of low-frequency Sonophoresis can be significantly enhanced by provision of nuclei for cavitation. In this study, we used two porous resins, Diaion HP20 and Diaion HP2MG (2MG), as cavitation nuclei. We measured the effect of these resins on cavitation using pitting of aluminum foil. 2MG showed a higher efficacy in enhancing cavitation compared with Diaion HP20. 2MG was also effective in enhancing transdermal mannitol transport. These results confirm that the addition of cavitation nuclei such as porous resins further increases the effect of low-frequency ultrasound on skin permeability.

Joseph Kost - One of the best experts on this subject based on the ideXlab platform.

  • bubble growth within the skin by rectified diffusion might play a significant role in Sonophoresis
    Journal of Controlled Release, 2007
    Co-Authors: Ilana Lavon, Nili Grossman, E. Kimmel, Joseph Kost, Giora Enden
    Abstract:

    Low frequency ultrasound has successfully been used for enhancing transdermal transport of a variety of different molecules. This phenomenon is referred to as Sonophoresis. Several attempts have been made to investigate the enhancing mechanism in order to modulate the overall process. In this study we assess whether rectified diffusion is a process that occurs within the skin, which could eventually lead to channeling and thereby to transdermal Sonophoresis. The model presented in this paper is based on the following postulate: gas bubbles are randomly distributed within the lipid bilayers of the stratum corneum (SC). As the skin is subjected to ultrasound, gas bubbles grow by rectified diffusion. During this period, bubbles may merge with the outer or inner boundaries of the SC, or merge with neighboring bubbles. Eventually, channels are created, allowing drugs to easily penetrate through the most significant barrier to transdermal delivery, the SC. As a result, transdermal transport rate is enhanced. In this work, a mathematical model has been formulated, in which permeability enhancement of the SC is linked to channels, possibly created by means of rectified diffusion. Sonophoresis may result from various mechanisms that act in synergy. The present model predicts that rectified diffusion might be one of the factors that lead to Sonophoresis during ultrasound treatment.

  • Bubble growth within the skin by rectified diffusion might play a significant role in Sonophoresis
    Journal of Controlled Release, 2007
    Co-Authors: Ilana Lavon, Nili Grossman, E. Kimmel, Joseph Kost, Giora Enden
    Abstract:

    Low frequency ultrasound has successfully been used for enhancing transdermal transport of a variety of different molecules. This phenomenon is referred to as Sonophoresis. Several attempts have been made to investigate the enhancing mechanism in order to modulate the overall process. In this study we assess whether rectified diffusion is a process that occurs within the skin, which could eventually lead to channeling and thereby to transdermal Sonophoresis. The model presented in this paper is based on the following postulate: gas bubbles are randomly distributed within the lipid bilayers of the stratum corneum (SC). As the skin is subjected to ultrasound, gas bubbles grow by rectified diffusion. During this period, bubbles may merge with the outer or inner boundaries of the SC, or merge with neighboring bubbles. Eventually, channels are created, allowing drugs to easily penetrate through the most significant barrier to transdermal delivery, the SC. As a result, transdermal transport rate is enhanced. In this work, a mathematical model has been formulated, in which permeability enhancement of the SC is linked to channels, possibly created by means of rectified diffusion. Sonophoresis may result from various mechanisms that act in synergy. The present model predicts that rectified diffusion might be one of the factors that lead to Sonophoresis during ultrasound treatment. © 2006 Elsevier B.V. All rights reserved.

  • ultrasound and transdermal drug delivery
    Drug Discovery Today, 2004
    Co-Authors: Ilana Lavon, Joseph Kost
    Abstract:

    Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Application of ultrasound to the skin increases its permeability (Sonophoresis) and enables the delivery of various substances into and through the skin. This review presents the main findings in the field of Sonophoresis, namely transdermal drug delivery and transdermal monitoring. Particular attention is paid to proposed enhancement mechanisms and future trends in the field of cutaneous vaccination and gene delivery.

  • low frequency Sonophoresis a review
    Advanced Drug Delivery Reviews, 2004
    Co-Authors: Samir Mitragotri, Joseph Kost
    Abstract:

    Application of ultrasound enhances skin permeability to a variety of molecules (Sonophoresis). The enhancement induced by ultrasound is particularly significant at low-frequencies (f<100 kHz, low-frequency Sonophoresis). This review summarizes mechanisms and applications of low-frequency Sonophoresis. In vitro, in vivo, as well as clinical studies demonstrating the effect of low-frequency ultrasound on transdermal drug delivery and glucose extraction are summarized. Mechanistic insights gained through a number of investigations are also reviewed. Finally, reports on the synergistic effect of low-frequency ultrasound with other enhancers including chemicals and iontophoresis are summarized.

  • Low-frequency Sonophoresis: A review
    Advanced Drug Delivery Reviews, 2004
    Co-Authors: Samir Mitragotri, Joseph Kost
    Abstract:

    Application of ultrasound enhances skin permeability to a variety of molecules (Sonophoresis). The enhancement induced by ultrasound is particularly significant at low-frequencies (f

Hyunjin Park - One of the best experts on this subject based on the ideXlab platform.

  • Transdermal Drug Delivery Using a Specialized Cavitation Seed for Ultrasound
    IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control, 2019
    Co-Authors: Donghee Park, H. Park, Ji Young Jang, Unchul Shin, Gillsoo Song, Hyunjin Park
    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 μm 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.

  • Sonophoresis using ultrasound contrast agents dependence on concentration
    PLOS ONE, 2016
    Co-Authors: Donghee Park, Gillsoo Song, Yongjun Jo, Byungjo Jung, Hyunjin Park
    Abstract:

    Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of Sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of Sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by Sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of Sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that Sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using Sonophoresis with microbubbles depends on the concentration of microbubbles in case stable cavitation is predominant.

  • Sonophoresis in transdermal drug deliverys
    Ultrasonics, 2014
    Co-Authors: Donghee Park, Hyunjin Park
    Abstract:

    Abstract Transdermal drug delivery (TDD) has several significant advantages compared to oral drug delivery, including elimination of pain and sustained drug release. However, the use of TDD is limited by low skin permeability due to the stratum corneum (SC), the outermost layer of the skin. Sonophoresis is a technique that temporarily increases skin permeability such that various medications can be delivered noninvasively. For the past several decades, various studies of Sonophoresis in TDD have been performed focusing on parameter optimization, delivery mechanism, transport pathway, or delivery of several drug categories including hydrophilic and high molecular weight compounds. Based on these various studies, several possible mechanisms of Sonophoresis have been suggested. For example, cavitation is believed to be the predominant mechanism responsible for drug delivery in Sonophoresis. This review presents details of various studies on Sonophoresis including the latest trends, delivery of various therapeutic drugs, Sonophoresis pathways and mechanisms, and outlook of future studies.

  • Sonophoresis using ultrasound contrast agents for transdermal drug delivery an in vivo experimental study
    Ultrasound in Medicine and Biology, 2012
    Co-Authors: Donghee Park, Kyu Sil Choi, Hyunjin Park
    Abstract:

    Abstract Sonophoresis temporally increases skin permeability such that various medications can be delivered noninvasively. Previous Sonophoresis studies have suggested that cavitation plays an important role in enhancing transdermal drug delivery (TDD). In this study, the feasibility of controlled cavitation using ultrasound contrast agents (UCAs) at high frequency was explored through in vivo experiments in a rat model. Two commercially available UCAs, SonoVue® and Definity®, were used at 2.47 MHz and 1.12 MHz, respectively. Fluorescein isothiocyanate (FITC)-dextran with 0.1% UCA was used as the drug to be delivered through the skin. Ultrasound with a 10 ms pulse and a 1% duty cycle at 1 MPa acoustic pressure for 30 min was applied in all sonication sessions. The efficacy of Sonophoresis with UCAs was quantitatively analyzed using an optical imaging system that was used to count photons emitted from fluorescein. The results showed that the proposed Sonophoresis method significantly improved drug penetration compared with the traditional Sonophoresis method with 4 kD, 20 kD and 150 kD FITC-dextrans at 1.12 MHz, and with 4 kD and 20 kD FITC-dextrans at 2.47 MHz. Sonophoresis for TDD was performed more effectively with the aid of UCAs. Sonophoresis with UCAs has excellent potential for broad applications in drug delivery for diseases requiring the chronic administration of medications such as diabetes.

Donghee Park - One of the best experts on this subject based on the ideXlab platform.

  • Transdermal Drug Delivery Using a Specialized Cavitation Seed for Ultrasound
    IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control, 2019
    Co-Authors: Donghee Park, H. Park, Ji Young Jang, Unchul Shin, Gillsoo Song, Hyunjin Park
    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 μm 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.

  • transdermal delivery of macromolecule using Sonophoresis with cavitation seed in vivo study
    Internaltional Ultrasonics Symposium, 2017
    Co-Authors: Hyeon Jin Park, Donghee Park, Ji Young Jang, Bomi Hong, Yujin Park
    Abstract:

    Sonophoresis which utilizes ultrasound for transdermal drug delivery (TDD), can increase the skin permeability and improve the efficiency of drug delivery to various drugs. In addition, the addition of microbubbles in Sonophoresis accelerate and increase an efficiency of drug delivery. The cavitation induced by Sonophoresis with microbubbles on the skin surface may cause disordering of the lipid bilayers and the formation of aqueous channels. However, commercial microbubble such as ultrasound contrast agents (UCA) have limitation for Sonophoresis, because mixed microbubbles is uniformly positioned in water based solution, not on skin surface. Accordingly, we hypothesized that if the most of engineered microbubbles can be located on the skin surface, cavitation effect will be maximized for TDD. We propose an advanced concept microbubble specialized in Sonophoresis as an alternative cavitation seed, which can be sank near skin surface by gravity. We manufactured the cavitation seed specialized in Sonophoresis which consist of liquid phase perfluorohexane core. In order to make sure possibility of macromolecules delivery using Sonophoresis with cavitation seed, we performed in vivo experiment using 150kDa of FITC-labeled dextran (FD). The delivered fluorescent into the skin was quantitatively analyzed by an optical imaging system and confocal microscope. In the results, FITC-labeled dextran, 150 kDa, was delivered to 600 μm depth under the skin, and average total flux in ROI was increased 6.4 fold in Sonophoresis with cavitation seed group more than diffusion groups. In conclusion, simultaneous application of ultrasound and cavitation seed for TDD demonstrated high efficiency of TDD and possibility of macromolecule delivery into the skin. We confidently believe this technology has the potential in various fields related with TDD.

  • Sonophoresis using ultrasound contrast agents dependence on concentration
    PLOS ONE, 2016
    Co-Authors: Donghee Park, Gillsoo Song, Yongjun Jo, Byungjo Jung, Hyunjin Park
    Abstract:

    Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of Sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of Sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by Sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of Sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that Sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using Sonophoresis with microbubbles depends on the concentration of microbubbles in case stable cavitation is predominant.

  • Sonophoresis in transdermal drug deliverys
    Ultrasonics, 2014
    Co-Authors: Donghee Park, Hyunjin Park
    Abstract:

    Abstract Transdermal drug delivery (TDD) has several significant advantages compared to oral drug delivery, including elimination of pain and sustained drug release. However, the use of TDD is limited by low skin permeability due to the stratum corneum (SC), the outermost layer of the skin. Sonophoresis is a technique that temporarily increases skin permeability such that various medications can be delivered noninvasively. For the past several decades, various studies of Sonophoresis in TDD have been performed focusing on parameter optimization, delivery mechanism, transport pathway, or delivery of several drug categories including hydrophilic and high molecular weight compounds. Based on these various studies, several possible mechanisms of Sonophoresis have been suggested. For example, cavitation is believed to be the predominant mechanism responsible for drug delivery in Sonophoresis. This review presents details of various studies on Sonophoresis including the latest trends, delivery of various therapeutic drugs, Sonophoresis pathways and mechanisms, and outlook of future studies.

  • Sonophoresis using ultrasound contrast agents for transdermal drug delivery an in vivo experimental study
    Ultrasound in Medicine and Biology, 2012
    Co-Authors: Donghee Park, Kyu Sil Choi, Hyunjin Park
    Abstract:

    Abstract Sonophoresis temporally increases skin permeability such that various medications can be delivered noninvasively. Previous Sonophoresis studies have suggested that cavitation plays an important role in enhancing transdermal drug delivery (TDD). In this study, the feasibility of controlled cavitation using ultrasound contrast agents (UCAs) at high frequency was explored through in vivo experiments in a rat model. Two commercially available UCAs, SonoVue® and Definity®, were used at 2.47 MHz and 1.12 MHz, respectively. Fluorescein isothiocyanate (FITC)-dextran with 0.1% UCA was used as the drug to be delivered through the skin. Ultrasound with a 10 ms pulse and a 1% duty cycle at 1 MPa acoustic pressure for 30 min was applied in all sonication sessions. The efficacy of Sonophoresis with UCAs was quantitatively analyzed using an optical imaging system that was used to count photons emitted from fluorescein. The results showed that the proposed Sonophoresis method significantly improved drug penetration compared with the traditional Sonophoresis method with 4 kD, 20 kD and 150 kD FITC-dextrans at 1.12 MHz, and with 4 kD and 20 kD FITC-dextrans at 2.47 MHz. Sonophoresis for TDD was performed more effectively with the aid of UCAs. Sonophoresis with UCAs has excellent potential for broad applications in drug delivery for diseases requiring the chronic administration of medications such as diabetes.