Porous Resins as a Cavitation Enhancer for Low‐frequency Sonophoresis

Terahara, Takaaki; Mitragotri, Samir; Langer, Robert

doi:10.1002/jps.10080

Cited by 35 publications

(22 citation statements)

References 15 publications

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“…Griffin & Touchstone, 1972;Johnson et al, 1996;Kleinkort & Wood, 1975;Kost & Langer, 1993;Kost et al, 1996;Kost et al, 1999;Kost et al, 2000;Le et al, 2000;Machluf & Kost, 1993;Menon et al, 1994Mitragotri, 1995Mitragotri & Langer 1995b;Mitragotri et al 1996a, b Mitragotri, etal, 1997Mitragotri etal, 2000, b;Mitragotri & Kost, 2000a. b;Quillen, 1980;Roitt et al, 1998;Terahara et al, 2002Tang et al, 2002;Tang et al, 2001;Tezel et al 2002a, b;Tezel etal, 2003;Tachibana, 1992;Tachibana &Tachibana, 1993Tachibana & Tachibana 1991Williams, 1990;Alvarez-Romania/., 2003;Merrino et al, 2003;Merriono et al, 2003;Weimann et al, 2002;Joshi & Raje, 2002;Machet & Boucaud, 2002). This type of enhancement is termed sonophoresis, indicating the enhanced transport of molecules under the influence of ultrasound.…”

Section: Ultrasound In Medical Applicationmentioning

confidence: 89%

Low-Frequency Sonophoresis: Ultrasound-Mediated Transdermal Drug Delivery

Mitragotri¹

2006

Emerging Therapeutic Ultrasound

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Transdermal drug delivery offers an attractive mode of drug administration. However, applications of transdermal drug delivery are limited due to low skin permeability. Application of ultrasound enhances skin permeability to a variety of molecules (sonophoresis). The enhancement induced by ultrasound is particularly significant at low frequencies (/ < 100 kHz, low-frequency sonophoresis). This chapter 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. Reports on the synergistic effect of low-frequency ultrasound with other enhancers including chemicals and iontophoresis are also summarized. Finally, safety considerations of low-frequency sonophoresis are reviewed.

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Section: Ultrasound In Medical Applicationmentioning

confidence: 89%

Low-Frequency Sonophoresis: Ultrasound-Mediated Transdermal Drug Delivery

Mitragotri¹

2006

Emerging Therapeutic Ultrasound

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“…However, tissue heating can be accompanied by adverse bioeffects within the SC, ranging from lipid-associated conformational alterations to irreversible structural perturbations [48], even when skin temperatures are kept below 65 °C. To avoid these adverse effects during sonophoresis, ultrasound is commonly applied in a pulsed mode to minimize tissue heating [16, 18, 22, 23, 49, 50]. …”

Section: Discussionmentioning

confidence: 99%

“…These techniques include the addition of cavitation nuclei, such as insoluble porous resins [23], to the coupling medium outside the skin or simultaneous application of high-frequency ultrasound to nucleate small bubbles near the skin surface, which then cavitate in response to the lower-frequency ultrasound used for sonophoresis [24]. For HFS treatments, although cavitation activity within skin contributes to the overall permeabilization, optimizing and controlling cavitation within skin tissue may be challenging due to the sparse preexistence of gas bodies and the spatially variable threshold to initiate cavitation activity in living tissue [52].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, theoretical [21] and experimental [22] investigations have indicated that the permeabilization effect from inertial cavitation during LFS is primarily due to microjet formations, manifested during the asymmetric collapse of bubbles near the skin surface, that impact and locally perturb the SC. Exploitation of this well characterized mechanism has led LFS treatments to provide a greater, although reversible, permeabilization effect while also significantly reducing treatment times [23, 24]. …”

Section: Introductionmentioning

confidence: 99%

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Relations between acoustic cavitation and skin resistance during intermediate- and high-frequency sonophoresis

Rich

Hoerig

Rao

et al. 2014

Journal of Controlled Release

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Enhanced skin permeability is known to be achieved during sonophoresis due to ultrasound-induced cavitation. However, the mechanistic role of cavitation during sonophoresis has only been extensively investigated for low-frequency (LFS, <100 kHz) applications. Here, mechanisms of permeability-enhancing stable and inertial cavitation were investigated by passively monitoring subharmonic and broadband emissions arising from cavitation isolated within or external to porcine skin in vitro during intermediate- (IFS, 100–700 kHz) and high-frequency sonophoresis (HFS, >1 MHz). The electrical resistance of skin, a surrogate measure of the permeability of skin to a variety of compounds, was measured to quantify the reduction and subsequent recovery of the skin barrier during and after exposure to pulsed (1 second pulse, 20% duty cycle) 0.41 and 2.0 MHz ultrasound over a range of acoustic powers (0–21.7 W) for 30 minutes. During IFS, significant skin resistance reductions and acoustic emissions from cavitation were measured exclusively when cavitation was isolated outside of the skin. Time-dependent skin resistance reductions measured during IFS correlated significantly with subharmonic and broadband emission levels. During HFS, significant skin resistance reductions were accompanied by significant acoustic emissions from cavitation measured during trials that isolated cavitation activity either outside of skin or within skin. Time-dependent skin resistance reductions measured during HFS correlated significantly greater with subharmonic than with broadband emission levels. The reduction of the skin barrier due to sonophoresis was reversible in all trials; however, effects incurred during IFS recovered more slowly and persisted over a longer period of time than HFS. These results quantitatively demonstrate the significance of cavitation during sonophoresis and suggest that the mechanisms and post-treatment longevity of permeability enhancement due to IFS and HFS treatments are different.

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“…11 It may be possible to further improve skin permeabilization by incorporating a porous resin in the formulation that acts as a cavitation enhancer. 12 Crucially, the skin regenerates its barrier properties several hours after the end of sonication. 9 Sonophoretic systems are currently in various phases of preclinical testing.…”

Section: Sonophoretic Technologymentioning

confidence: 99%

Emerging Technologies in Transdermal Therapeutics

Meidan¹,

Michniak²

2004

American Journal of Therapeutics

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Until very recently, the only drugs that could permeate transdermally were those possessing a very narrow and specific combination of physicochemical properties. However, rapid advances in bioengineering have led to the emergence of various new "active" enhancement technologies designed to transiently circumvent the barrier function of the stratum corneum. These novel systems, using iontophoresis, sonophoresis, electroporation, or microneedle arrays, will greatly expand the range of drugs that can be delivered transdermally. Crucially, the delivery of macromolecules will become possible and the transdermal flux of other molecules could be enhanced by several orders of magnitude. This article sequentially reviews the basis of each of the new enhancement techniques and discusses how these emerging technologies will influence transdermal therapy in the coming years.

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Porous Resins as a Cavitation Enhancer for Low‐frequency Sonophoresis

Cited by 35 publications

References 15 publications

Low-Frequency Sonophoresis: Ultrasound-Mediated Transdermal Drug Delivery

Low-Frequency Sonophoresis: Ultrasound-Mediated Transdermal Drug Delivery

Relations between acoustic cavitation and skin resistance during intermediate- and high-frequency sonophoresis

Emerging Technologies in Transdermal Therapeutics

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