The effects of phonophoresis with corticosteroids: a controlled pilot study

Although physical therapists and physicians often treat patients with local musculoskeletal inflammation using topically applied steroids enhanced with ultrasound, there is a paucity of research confirming that phonophoresis significantly enhances drug diffusion. The purpose of this study was to determine if ultrasound enhances the diffusion of transdermally applied corticosteroids. Diffusion was measured secondarily in terms of collagen deposition [estimated by levels of hydroxyproline in polytetrafluroethylene (ePTFE) tubing] and cellular activity (measured by levels of DNA). Sixteen pieces of ePTFE tubing were subcutaneously implanted on the dorsum of five mini Yucatan pigs. Pairs of tubing were randomly assigned to sham control or treatment groups. Over the paired ePTFE tubes in the treatment groups, a single transdermal application of hydrocortisone acetate (HC) or dexamethasone (DX) was applied to the skin by rubbing, sonating with the drug mixed in the acoustic gel (1.5 W/cm2, 1 MHz, 5 minutes), or injecting the drug into the tubing. Four additional ePTFE tubes were threaded in the extremities, two submuscularly and two subtendinously, with random assignment to a sham control or a DX sonation treatment group. At the end of a week, the mean hydroxyproline levels in the swine were lower than expected (mean = 9.3 micrograms/cm compared to an expected mean = 22.2 micrograms/cm). Comparing the control and skin-applied groups with the injected and sonated treatment groups, the hydroxyproline was found to be 50% lower in the DX-injected, DX-sonated, and HC-injected sites. However, statistically there were no significant differences in DNA or hydroxyproline levels between the HC subcutaneous control and treatment groups or the DX submuscular and subtendinous groups. There was a significant main effect of group on hydroxyproline levels in the group of DX-treated, subcutaneously implanted ePTFE tubes (p = 0.001). Post hoc testing revealed a significant difference between the skin-rubbed and control groups together compared to the DX-injected and DX-sonated groups together (p = 0.001). These findings indicate that the effects of phonophoresed DX can be measured in terms of reduced collagen deposition as far down as the subcutaneous tissue but not in the submuscular or subtendinous tissue. However, a single application may not have a measurable effect on cellular activity after 7 days of healing. The unusually low level of hydroxyproline across all groups suggests that phonophoresis with steroids may have had a systemic as well as a local effect.