title: Enhanced therapeutic anti-inflammatory effect of betamethasone on topical administration with low-frequency, low-intensity (20 kHz, 100 mW/cm(2)) ultrasound exposure on carrageenan-induced arthritis in a mouse model.
abstract: The purpose of this work was to investigate whether low-frequency, low-intensity (20 kHz, <100 mW/cm(2), 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.
authors.affiliation: School of Pharmacy Institute for Drug Research, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Gadi
authors.initials: G
authors.lastname: Cohen
authors.affiliation: School of Pharmacy Institute for Drug Research, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Hiba
authors.initials: H
authors.lastname: Natsheh
authors.affiliation: School of Biomedical Engineering, Sciences and Heath Systems, Drexel University, Philadelphia, Pennsylvania, USA.
authors.forename: Youhan
authors.initials: Y
authors.lastname: Sunny
authors.affiliation: School of Biomedical Engineering, Sciences and Heath Systems, Drexel University, Philadelphia, Pennsylvania, USA. Electronic address: crb68@drexel.edu.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Bawiec
authors.affiliation: School of Pharmacy Institute for Drug Research, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Elka
authors.initials: E
authors.lastname: Touitou
authors.affiliation: Division of Rheumatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Lerman
authors.affiliation: School of Pharmacy Institute for Drug Research, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Philip
authors.initials: P
authors.lastname: Lazarovici
authors.affiliation: School of Biomedical Engineering, Sciences and Heath Systems, Drexel University, Philadelphia, Pennsylvania, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Lewin
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001168:Arthritis / Q000175:diagnosis* / Q000628:therapy*; D001623:Betamethasone / Q000008:administration & dosage*; D002351:Carrageenan; D003131:Combined Modality Therapy / Q000379:methods; D004357:Drug Synergism; D018274:Electroporation / Q000379:methods*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013010:Sonication / Q000295:instrumentation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D002351:Carrageenan; D001623:Betamethasone
keywords: Anti-inflammatory effect; Betamethasone; Carrageenan-induced arthritis; Low-frequency ultrasound; Near-infrared imaging; Topical delivery