Pulsed current iontophoresis of hyaluronic acid in living rat skin.

Hyaluronic acid (HA) is a natural glycosaminoglycan (GAG) used in treatment and prevention of different skin diseases and as a filler agent for improving wrinkles, scars, or increasing volumes [1]. Because of chemical structure, HA has to be injected repeatedly for many months [2], in tens or hundreds of sites [3], by experienced operators [4]. This feature contrasts with the needs of today’s busy and demanding world that ask for painless ‘‘lunchtime procedures’’ [4,5]. In this study we evaluated the efficacy of a powered pulsed current iontophoresis drug delivery system (Transderm Ionto System, Mattioli Engineering, McLean, VA, USA) approved for clinical use in humans by the US Food and Drug Administration (FDA, approval no. K042590, 10.14.2004), in delivering HA through living rat skin, following the procedure described in Ref. [6]. We applied 0.5 ml of fluorescent HA (mean molecular weight, MW 800 kDa; Molecular Probes, Carlsbad, CA, USA), at a final concentration of 2 mg/ml, or alternatively, 0.5 ml of stable, uniformly labeled radioactive [H]-HA (American Radiolabeled Chemicals, St. Louis, MO, USA) (250 mCi/g, 1 mCi/ml, mean MW, 800 kDa). [ H]-radioactivity is expressed as counts per minute (cpm). The applied volume (0.5 ml) was close to that routinely injected in patients (0.7 ml) [2]. Statistical analysis was performed using Student’s t-test. Data are presented as means S.D. (n = 3), and were considered significantly different when p < 0.05. First, we checked for modifications of skin structure following the electrically assisted procedure [6]. Although the device used in this study is