Dependence of low-frequency sonophoresis on ultrasound parameters; distance of the horn and intensity

Terahara, Takaaki; Mitragotri, Samir; Kost, Joseph; Langer, Robert

doi:10.1016/s0378-5173(01)00981-4

Cited by 80 publications

(46 citation statements)

References 15 publications

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“…Skin samples were treated in a similar fashion to previously reported methods [11,14,15]. Specifically, a 20 kHz horn (Sonics and Materials, Inc. Model VCX 500, Newtown, CT) and a 1 MHz horn (Therasound 3 Series, Richmar Corporation, Chattanooga, TN) were employed.…”

Section: Methodsmentioning

confidence: 99%

Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs

Schoellhammer

Srinivasan

Barman

et al. 2015

Journal of Controlled Release

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Low-frequency ultrasound presents an attractive method for transdermal drug delivery. The controlled, yet nonspecific nature of enhancement broadens the range of therapeutics that can be delivered, while minimizing necessary reformulation efforts for differing compounds. Long and inconsistent treatment times, however, have partially limited the attractiveness of this method. Building on recent advances made in this area, the simultaneous use of low- and high-frequency ultrasound is explored in a physiologically relevant experimental setup to enable the translation of this treatment to testing in vivo. Dual-frequency ultrasound, utilizing 20 kHz and 1 MHz wavelengths simultaneously, was found to significantly enhance the size of localized transport regions (LTRs) in both in vitro and in vivo models while decreasing the necessary treatment time compared to 20 kHz alone. Additionally, LTRs generated by treatment with 20 kHz + 1 MHz were found to be more permeable than those generated with 20 kHz alone. This was further corroborated with pore-size estimates utilizing hindered-transport theory, in which the pores in skin treated with 20 kHz + 1 MHz were calculated to be significantly larger than the pores in skin treated with 20 kHz alone. This demonstrates for the first time that LTRs generated with 20 kHz + 1 MHz are also more permeable than those generated with 20 kHz alone, which could broaden the range of therapeutics and doses administered transdermally. With regard to safety, treatment with 20 kHz + 1 MHz both in vitro and in vivo appeared to result in no greater skin disruption than that observed in skin treated with 20 kHz alone, an FDA-approved modality. This study demonstrates that dual-frequency ultrasound is more efficient and effective than single-frequency ultrasound and is well-tolerated in vivo.

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Section: Methodsmentioning

confidence: 99%

Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs

Schoellhammer

Srinivasan

Barman

et al. 2015

Journal of Controlled Release

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“…Sometimes chemical enhancers were used to further increase the permeability [102][103][104]. However, no significant transport of protein could be achieved until 10 years ago when Mitrogotri et al showed that low frequency ultrasound was much more effective than higher frequencies and provided evidence as to the mechanism involved [102][103][104][105][106][107][108][109][110][111][112][113][114]. Skin permeability increased with decreasing frequency, and with increasing time of exposure and intensity (beyond a threshold), thus identifying collapse cavitation as a causative mechanism [105][106][107]110,111,115].…”

Section: Transdermal Protein Delivery-mentioning

confidence: 99%

Ultrasonic drug delivery – a general review

Pitt

Husseini

Staples

2004

Expert Opinion on Drug Delivery

557

428

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Ultrasound (US) has an ever-increasing role in the delivery of therapeutic agents including genetic material, proteins, and chemotherapeutic agents. Cavitating gas bodies such as microbubbles are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilize cell membranes and disrupt the vesicles that carry drugs. Thus the presence of microbubbles enormously enhances delivery of genetic material, proteins and smaller chemical agents. Delivery of genetic material is greatly enhanced by ultrasound in the presence of microbubbles. Attaching the DNA directly to the microbubbles or to gas-containing liposomes enhances gene uptake even further. US-enhanced gene delivery has been studied in various tissues including cardiac, vascular, skeletal muscle, tumor and even fetal tissue. US-enhanced delivery of proteins has found most application in transdermal delivery of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; it also makes the cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has upon cells and drug-carrying vesicles.

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“…In fact, medical researchers have shown that low-frequency ultrasound is effective in enhancing transdermal transport of various molecules [1,10,11,16,17,19]. Within this work, they have demonstrated that the frequencies around 40 kHz have excellent transdermal propagation with minimal heating [17].…”

Section: Related Workmentioning

confidence: 73%

The sound of touch

Mujibiya

Cao

Tan

et al. 2013

Proceedings of the 2013 ACM International Conference on Interactive Tabletops and Surfaces

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Recent work has shown that the body provides an interesting interaction platform. We propose a novel sensing technique based on transdermal low-frequency ultrasound propagation. This technique enables pressure-aware continuous touch sensing as well as arm-grasping hand gestures on the human body. We describe the phenomena we leverage as well as the system that produces ultrasound signals on one part of the body and measures this signal on another. The measured signal varies according to the measurement location, forming distinctive propagation profiles which are useful to infer on-body touch locations and on-body gestures. We also report on a series of experimental studies with 20 participants that characterize the signal, and show robust touch and gesture classification along the forearm.

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Dependence of low-frequency sonophoresis on ultrasound parameters; distance of the horn and intensity

Cited by 80 publications

References 15 publications

Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs

Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs

Ultrasonic drug delivery – a general review

The sound of touch

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