A New Method for Percutaneous Drug Delivery by Thermo-Mechanical Fractional Injury.

Background and Objectives: Percutaneous drug delivery (PDD) is a means of increasing the uptake of topically applied agents into the skin. Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy. To evaluate the efficacy of pretreatment by thermomechanical fractional injury (TMFI) (Tixel®, Novoxel®, Israel) at low-energy settings in increasing the permeability of the skin to a known hydrophilic-photosensitizer medication, 5-amino-levulinic-acid hydrochloride (ALA) in compounded 20% ALA gel. To compare the effect of TMFI on ALA permeation into the skin in compounded gel to three commercial photosensitizing medications in different vehicles: ALA microemulsion gel, methyl-amino-levulinic-acid hydrochloride (MAL) cream, and ALA hydroalcoholic solution.
Study Design/materials and Methods: Five healthy subjects were treated in two separate experiments and on a total of 136 test sites, with four topical photosensitizer preparations as follows: compounded 20% ALA gel prepared in a good manufacturing practice (GMP)-certified pharmacy (Super-Pharm Professional, Israel), 10% ALA microemulsion gel (Ameluz®, Biofrontera Bioscience GmbH, Leverkusen, Germany), 16.8% MAL cream (Metvix®, Galderma, Lausanne, Switzerland), and 20% ALA hydroalcoholic solution (Levulan Kerastick®, DUSA Pharmaceuticals, Inc., Wilmington, MA, USA). The dermal sites were pretreated by Tixel® (Novoxel® Ltd., Israel) prior to topical drug application. One site was untreated to serve as control. Protoporphyrin IX (PpIX) fluorescence intensity readouts were taken immediately and 1, 2, 3, 4, and 5 hours posttreatment.
Results: The highest average PpIX fluorescence intensity measurements were obtained for the compounded 20% ALA gel following pre-treatment by TMFI at 6 milliseconds pulse duration. After 2 and 3 hours, TMFI-treated sites exhibited an increased hourly rate in readouts of FluoDerm units, which were 156-176% higher than the control rates (P ≤ 0.004). TMFI pre-treatment did not enhance the percutaneous permeation of either ALA or MAL following the microemulsion gel, hydroalcoholic solution, and cream applications.
Conclusions: Pretreatment with low-energy TMFI at a pulse duration of 6 milliseconds increased the percutaneous permeation of ALA linearly over the first 5 hours from application when the compounded 20% ALA gel was used. Formulation characteristics have substantial influence on the ability of TMFI pretreatment to significantly increase the percutaneous permeation of ALA and MAL. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
(© 2019 Wiley Periodicals, Inc.)