Thermo-Mechanical Fractional Injury Enhances Skin Surface- and Epidermis- Protoporphyrin IX Fluorescence: Comparison of 5-Aminolevulinic Acid in Cream and Gel Vehicles
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Thermo-Mechanical Fractional Injury Enhances Skin Surface- and Epidermis- Protoporphyrin IX Fluorescence : Comparison of 5-Aminolevulinic Acid in Cream and Gel Vehicles. / Foged, Camilla; Haedersdal, Merete; Bik, Liora; Dierickx, Christine; Phillipsen, Peter A.; Togsverd-Bo, Katrine.
I: Lasers in Surgery and Medicine, Bind 53, Nr. 5, 2021, s. 622-629.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Thermo-Mechanical Fractional Injury Enhances Skin Surface- and Epidermis- Protoporphyrin IX Fluorescence
T2 - Comparison of 5-Aminolevulinic Acid in Cream and Gel Vehicles
AU - Foged, Camilla
AU - Haedersdal, Merete
AU - Bik, Liora
AU - Dierickx, Christine
AU - Phillipsen, Peter A.
AU - Togsverd-Bo, Katrine
N1 - Publisher Copyright: © 2020 Wiley Periodicals LLC
PY - 2021
Y1 - 2021
N2 - 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 TMFI-mediated 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.
AB - 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 TMFI-mediated 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.
KW - 5-aminolevulinic acid
KW - actinic keratoses
KW - fluorescence microscopy
KW - photodynamic therapy
KW - Protoporphyrin IX
KW - stratum corneum
KW - thermo-mechanical fractional injury
KW - thermo-mechanical system
KW - vehicle viscosity
U2 - 10.1002/lsm.23326
DO - 10.1002/lsm.23326
M3 - Journal article
C2 - 33001491
AN - SCOPUS:85091746195
VL - 53
SP - 622
EP - 629
JO - Lasers in Surgery and Medicine
JF - Lasers in Surgery and Medicine
SN - 0196-8092
IS - 5
ER -
ID: 302458711