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

Abstract

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.

Wound Healing Process After Thermomechanical Skin Ablation

“…Besides skin ablation, TMA causing a low‐energy thermal decomposition of the stratum corneum can enhance the transepidermal penetration of substances 6; recently proved for botulinum toxin and 5‐amino‐levulinic‐acid 12,13. These findings, showing an increased permeability of the epidermis after TMA, could maybe be extrapolated for aesthetic applications, like platelet‐rich‐plasma treatments.…”

Thermomechanical Ablation‐Assisted Photodynamic Therapy for the Treatment of Acne Vulgaris. A Retrospective Chart Review of 30 Patients

“…Compared with lasers, mainly CO 2 lasers, the effect of TMA is more superficial [17,18]. However, pre‐treatment with low‐energy TMA was shown to increase the percutaneous permeation of compounded 20% ALA gel linearly over the first 5 hours from application, resulting in higher average PpIX fluorescence intensity measurements compared with only topical ALA application [17]. This was the rationale of our TMA‐assisted PDT for our acne vulgaris patient.…”

Ablative fractional resurfacing with laser‐facilitated steroid delivery for burn scar management: Does the depth of laser penetration matter?

“…Energies between 40 and 60 mJ are usually combined with a density of 5%, 70–80 mJ with a density of 3%, and 90–150 mJ with a density of 1% (with the DeepFX™ handpiece). Laser facilitated drug delivery of corticosteroids (Kenacort A40) topically and/or by intralesional injection (of hypertrophic/nodular areas) following treatment of hypertrophic burn scars with the CO 2 ‐AFL Ultrapulse® represents part of our standard treatment protocol . Depending on the extent of the required intervention, all procedures (laser and surgical reconstructive treatments) are performed under local or general anesthesia in our dedicated burns theatre within the Burns Unit of CRGH.…”