Thermo‐Mechanical Fractional Injury Enhances Skin Surface‐ and Epidermis‐ Protoporphyrin IX Fluorescence: Comparison of 5‐Aminolevulinic Acid in Cream and Gel Vehicles

Abstract

Background and Objectives: Thermo-mechanical fractional injury (TMFI) impacts the skin barrier and may increase cutaneous drug uptake. This study investigated the potential of TMFI in combination with 5-aminolevulinic acid (ALA) cream and gel formulations to enhance Protoporphyrin IX (PpIX) fluorescence at the skin surface and in the skin. Study Design/Materials and Methods: In healthy volunteers (n = 12) a total of 144 test areas were demarcated on the upper back. Test areas were randomized to (i) TMFI (6 milliseconds, 400 µm at a single pass) or no pretreatment and (ii) 20% ALA in cream or gel formulations. Skin surface PpIX fluorescence was quantified by PpIX fluorescence photography and photometry in 30-minute intervals until 3 hours. PpIX fluorescence microscopy quantified separate PpIX fluorescence in the epidermis, and in superficial-, mid-, and deep-dermis from punch biopsies sampled after 3 hours of ALA incubation. Local skin reactions (LSR) and pain intensities (numerical rating scale 0-10) were evaluated immediately, at 3 hours and 14 days after the intervention. Results: TMFI exposure before photosensitizer application significantly increased skin surface PpIX fluorescence, both for ALA cream (TMFI-ALA-cream 7848 arbitrary units [AU] vs. ALA-cream 5441 AU, 3 hours, P < 0.001) and ALA gel (TMFI + ALA-gel 4591 AU vs. ALA-gel 3723 AU, 3 hours, P < 0.001). The TMFImediated increase in PpIX fluorescence was similar for ALA-cream and -gel formulations (P = 0.470) at the skin surface. In the epidermis, PpIX fluorescence intensities increased from combination treatment with TMFI and ALA-cream (TMFI + ALA-cream 421 AU vs. ALA-cream 293 AU, P = 0.034) but not from combination with TMFI and ALA-gel (TMI + ALA-gel 264 AU vs. ALA-gel 261 AU, P = 0.791). Dermal fluorescence intensities (superficial-, mid-, or deep dermis) were unaffected by TMFI pretreatment in both ALA-cream and ALA-gel exposed skin (P = 0.339). ALA-cream generally induced higher PpIX fluorescence intensities than ALA-gel (skin surface P < 0.001 and epidermis P < 0.03). TMFI induced low pain intensities (median 3) and mild LSR that were resolved at 14 days follow-up. Conclusion: Given the present study design, TMFI, in combination with the standardized application of 20% ALA cream and gel formulations, significantly enhanced skin surface PpIX fluorescence compared to no pretreatment. Additionally, TMFI increased epidermal PpIX fluorescence combined with 20% ALA cream vehicle. Thus, TMFI pretreatment and formulation characteristics exert influence on PpIX fluorescence intensities in normal skin. Lasers Surg. Med.

Treatment of periorbital wrinkles using thermo‐mechanical fractional injury therapy versus fractional non‐ablative 1565 nm laser: A comparative prospective, randomized, double‐arm, controlled study

“…TMFI technology is an excellent modality for drug delivery owing to its formation of micronsized wells in the epidermis lined by a thin rim of coagulation. 11,[27][28][29] As wrinkling in the periorbital region is exacerbated by constant contraction of the orbicularis oculi muscles with facial expression, the use of TMFI technology to deliver botulinum toxin may achieve a more profound improvement, by both diminishing muscle contraction and stimulating collagen production and remodeling in a region where the skin is thinnest.…”

“…In this study, we demonstrate that the TMFI device is effective in improving periorbital wrinkles with minimal AEs, and recovery time. TMFI technology is an excellent modality for drug delivery owing to its formation of micron‐sized wells in the epidermis lined by a thin rim of coagulation 11,27–29 …”

5-Aminolevulinic Acid and Red Led in Endodontics: A Narrative Review and Case Report

“…5-aminolevulinic acid (5-ALA) is an intrinsic photosensitizing agent different from phenothiazine derivatives such as toluidine blue and methylene blue, as it is converted in situ into an endogenous substance essential for the formation of the heme group, protoporphyrin IX (PpIX) a powerful photosensitizing agent [ 85 ]. This ALA photosensitizing agent and its derivatives have been used for many years with excellent efficacy in antibacterial therapy and in many cancerous and pre-cancerous diseases, in dermatology and in disease of the oral cavity [ 86 , 87 , 88 , 89 ]. Moreover, it is a natural molecule that has been extensively studied in other research fields such as agriculture and biotechnology [ 90 ].…”

Efficacy and safety of thermomechanical fractional injury‐assisted corticosteroid delivery versus intralesional corticosteroid injection for the treatment of hypertrophic scars: A randomized split‐scar trial

“…5,7 Thermomechanical fractional injury (TMFI) facilitates the transcutaneous absorption of topical medications via the creation of micropores through the stratum corneum. [8][9][10][11] This relatively novel technique uses a heated (400°C) titanium medical grade tip comprising of 81 (9 × 9) pyramid-shaped micro-pins covering an area of 1 cm 2 . The handpiece is placed vertically on the skin and when activated the tip travels at a preset speed and recedes in an automated fashion.…”

“…Thermomechanical fractional injury (TMFI) facilitates the transcutaneous absorption of topical medications via the creation of micropores through the stratum corneum 8–11 . This relatively novel technique uses a heated (400°C) titanium medical grade tip comprising of 81 (9 × 9) pyramid‐shaped micro‐pins covering an area of 1 cm 2 .…”