TY - JOUR
T1 - Enhanced Therapeutic Anti-Inflammatory Effect of Betamethasone on Topical Administration with Low-Frequency, Low-Intensity (20 kHz, 100 mW/cm2) Ultrasound Exposure on Carrageenan-Induced Arthritis in a Mouse Model
AU - Cohen, Gadi
AU - Natsheh, Hiba
AU - Sunny, Youhan
AU - Bawiec, Christopher R.
AU - Touitou, Elka
AU - Lerman, Melissa A.
AU - Lazarovici, Philip
AU - Lewin, Peter A.
N1 - Publisher Copyright:
© 2015 World Federation for Ultrasound in Medicine & Biology.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - The purpose of this work was to investigate whether low-frequency, low-intensity (20 kHz, <100 mW/cm2, spatial-peak, temporal-peak intensity) ultrasound, delivered with a lightweight (<100 g), tether-free, fully wearable, battery-powered applicator, is capable of reducing inflammation in a mouse model of rheumatoid arthritis. The therapeutic, acute, anti-inflammatory effect was estimated from the relative swelling induced in mice hindlimb paws. In an independent, indirect approach, the inflammation was bio-imaged by measuring glycolytic activity with near-infrared labeled 2-deoxyglucose. The outcome of the experiments indicated that the combination of ultrasound exposure and topical application of 0.1% (w/w) betamethasone gel resulted in statistically significantly (p < 0.05) enhanced anti-inflammatory activity in comparison with drug or ultrasound treatment alone. The present study underscores the potential benefits of low-frequency, low-intensity ultrasound-assisted drug delivery. However, the proof of concept presented indicates the need for additional experiments to systematically evaluate and optimize the potential of, and the conditions for, tolerable low-frequency, low-intensity ultrasound-promoted non-invasive drug delivery.
AB - The purpose of this work was to investigate whether low-frequency, low-intensity (20 kHz, <100 mW/cm2, spatial-peak, temporal-peak intensity) ultrasound, delivered with a lightweight (<100 g), tether-free, fully wearable, battery-powered applicator, is capable of reducing inflammation in a mouse model of rheumatoid arthritis. The therapeutic, acute, anti-inflammatory effect was estimated from the relative swelling induced in mice hindlimb paws. In an independent, indirect approach, the inflammation was bio-imaged by measuring glycolytic activity with near-infrared labeled 2-deoxyglucose. The outcome of the experiments indicated that the combination of ultrasound exposure and topical application of 0.1% (w/w) betamethasone gel resulted in statistically significantly (p < 0.05) enhanced anti-inflammatory activity in comparison with drug or ultrasound treatment alone. The present study underscores the potential benefits of low-frequency, low-intensity ultrasound-assisted drug delivery. However, the proof of concept presented indicates the need for additional experiments to systematically evaluate and optimize the potential of, and the conditions for, tolerable low-frequency, low-intensity ultrasound-promoted non-invasive drug delivery.
KW - Anti-inflammatory effect
KW - Betamethasone
KW - Carrageenan-induced arthritis
KW - Low-frequency ultrasound
KW - Near-infrared imaging
KW - Topical delivery
UR - http://www.scopus.com/inward/record.url?scp=84938199600&partnerID=8YFLogxK
U2 - 10.1016/j.ultrasmedbio.2015.04.009
DO - 10.1016/j.ultrasmedbio.2015.04.009
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C2 - 26003010
AN - SCOPUS:84938199600
SN - 0301-5629
VL - 41
SP - 2449
EP - 2457
JO - Ultrasound in Medicine and Biology
JF - Ultrasound in Medicine and Biology
IS - 9
ER -
