“SonoBandage” a transdermal ultrasound drug delivery system for peripheral neuropathy

Abstract

Peripheral neuropathy (PN) is a difficult disease to manage. Symptomatic treatment focuses primarily on pain relief, using NSAIDs, opioids, tri-cyclic antidepressants, and selective serotonin norepinephrine reuptake inhibitors. There is potential for ultrasound transdermal drug delivery to improve the quality of care provided to patients with PN, since it is well-suited to peripheral nerves which are close to the skin. In addition, targeted delivery avoids many of the systemic consequences of taking a drug. We developed a wearable ultrasound drug delivery system called “SonoBandage” that combines low-impedance miniaturization of ultrasound transducer, RF electronics, and battery power supply, with a novel hydrogel coupling bandage loaded with salicylic acid NSAID. The design of the SonoBandage allows the device to be used over a range of ultrasound frequencies (0.1–3 MHz), intensities (0.1–3 W/cm2), and durations (0.25–4 h) increasing system flexibility for drug delivery protocols. The SonoBandage with NSAID was evaluated on a bench-top model with freshly harvested porcine skin and synthetic biomimetic human skin membrane (Millipore Inc). Across the n = 40 samples studied, salicylic acid drug flux was increased by 2–20x as compared to control samples (p < 0.01) after 1–4 h of ultrasound treatment. SonoBandage has potential to be used as a practical NSAID delivery platform for peripheral neuropathy.

<p>Low-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment</p>

“… 7 Low frequency ultrasound (LFU) waves were previously applied to enhance the transdermal delivery of various drugs like caffeine, fentanyl and insulin. 18 , 19 On the other hand, the transdermal permeation of other drugs like salicylic acid 20 and ondansetron hydrochloride 10 was promoted following the application of high frequency ultrasound (HFU) waves. Aldwaikat et al 21 reported that drug enhancement ratio is inversely correlated to the ultrasound frequency.…”

Sustained Acoustic Medicine Combined with A Diclofenac Ultrasound Coupling Patch for the Rapid Symptomatic Relief of Knee Osteoarthritis: Multi-Site Clinical Efficacy Study

“…This outcome may be explained by increased penetration of diclofenac into the joint space leading to inhibition of COX1 and COX2 pathways [ 20 , 38 ], thus relieving the inflammatory response in the joint. Masterson et al (2020) demonstrated SAM increased transdermal diclofenac delivery 3.8 fold greater than topical application alone [ 51 ], which were similar to the results of transdermal salicylic acid delivery with SAM by Langer et al (2013) [ 49 ]. The sustained treatment and continued pain reduction over the 7-days suggest the potential of lower levels of cytokines to retain pain at a decreased intensity.…”

“…SAM applies continuous long-duration ultrasound along with localized delivery of diclofenac to decrease patients’ knee OA pain and improve joint function. In prior preclinical research, SAM has demonstrated the 3.8x increase of diclofenac penetration into and across the skin [ 49 ], along with drug delivery enhancement of other drugs over 4-hour treatment protocols [ 49 , 50 ].…”

Low-Intensity Continuous Ultrasound Therapies—A Systematic Review of Current State-of-the-Art and Future Perspectives

“…US offers a viable alternative to current technologies due to its diverse bioeffects on skin [ 34 , 130 , 131 , 133 ]. Sonophoresis is driven by the collapsing or imploding of unstable high-energy bubbles generating localized shockwaves and cavitation.…”

“…[ 140 ] Langer et al used a long-duration LICUS approach to study the penetration of salicylic acid in hydrogel transdermal drug delivery in vitro. Their SonoBandage system applied US at 10%, 50%, and 100% duty cycle at frequencies of 175 kHz and 3 MHz for 1 and 4 h. The study found a significant increase in drug penetration using LICUS for 4 h relative to non-treated controls [ 133 ]. Similarly, Masterson et al investigated diclofenac sodium penetration through a hydrogel stack using long-duration LICUS at 3 MHz, 0.132 W/cm 2 for 4 h. They reported a 3.8-fold higher drug penetration through a hydrogel stack mimicking the ex vivo transdermal model [ 141 ].…”