Transdermal bFGF delivery using low-frequency sonophoresis: An innovative potential therapy for osteoradionecrosis of jaws

Abstract

Osteoradionecrosis of jaws (ORNJ) is a serious complication of radiotherapy for patients with head and neck cancer. As of yet, no universally accepted treatment exists for this chronic pathologic condition. It has been shown that ultrasound is an effective, noninvasive adjunctive therapy in ORNJ, as ultrasound can result in the increase of angiogenesis and bone production, which are essential for ORNJ healing. Recently, low-frequency ultrasound has been demonstrated to enhance the transdermal delivery of macromolecules and hydrophilic drugs (low-frequency sonophoresis, LFS). As a biological macromolecule, basic fibroblast growth factor (bFGF) also has potential osteoinductive and angiogenic properties. Herein, we present a hypothesis that LFS-mediated transdermal bFGF delivery is capable of improving the healing of ORNJ and will be a new effective adjunctive therapy to surgery. This treatment combines low-frequency ultrasound with bFGF to respectively promote vascularly compromised bone and soft tissue wound healing, and is expected to be more effective than ultrasound therapy alone.

Localized Drug Delivery Systems: An Update on Treatment Options for Head and Neck Squamous Cell Carcinomas

“…Sonophoresis has also been investigated for skin and cervical cancer xenograft models with chemotherapeutic drugs such as cisplatin [ 113 ]. It has not been directly used for HNSCC; however, low frequency sonophoresis with fibroblast growth factor has been proposed as an adjunct to surgery in the treatment of osteoradionecrosis of the jaw [ 114 ].…”

Simulation of Low-Frequency Sonophoretic Piezoelectric Transducer Applied over Human Skin

“…The active methods of stimulation include iontophoresis [8], electroporation [9], photomechanical waves or lasers [10], and sonophoresis [11]. Besides transdermal drug delivery, sonophoresis is found in various other medical applications too, i.e., it is used to promote drug release in the digestive tract through an endoscope [12], dental applications [13], body contouring [14], wound healing [15], arthritis [16], etc.…”

“…Permeability of human skin depends on its thickness, which is different at different sites of the human body [13], as well as in race, age group, and gender [14]. For reasons of practical convenience, we considered the site of the volar forearm where the average thickness of the epidermis is 0.1 mm [15], and in this simulation, the acoustic pressure is measured at the lower end of epidermis as shown in Figure 1.…”