Enhanced and Sustained Cutaneous Delivery of Vismodegib by Ablative Fractional Laser and Microemulsion Formulation
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Enhanced and Sustained Cutaneous Delivery of Vismodegib by Ablative Fractional Laser and Microemulsion Formulation. / Olesen, Uffe Høgh; Clergeaud, Gael; Hendel, Kristoffer Kjærgaard; Yeung, Kelvin; Lerche, Catharina Margrethe; Andresen, Thomas Lars; Haedersdal, Merete.
I: Journal of Investigative Dermatology, Bind 140, Nr. 10, 2020, s. 2051-2059.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Enhanced and Sustained Cutaneous Delivery of Vismodegib by Ablative Fractional Laser and Microemulsion Formulation
AU - Olesen, Uffe Høgh
AU - Clergeaud, Gael
AU - Hendel, Kristoffer Kjærgaard
AU - Yeung, Kelvin
AU - Lerche, Catharina Margrethe
AU - Andresen, Thomas Lars
AU - Haedersdal, Merete
PY - 2020
Y1 - 2020
N2 - Oral administration of vismodegib for basal cell carcinoma treatment is limited by significant class-specific systemic side effects. We investigated the approach of combining ablative fractional laser–assisted drug delivery with an extended-release microemulsion formulation of vismodegib to provide efficient cutaneous delivery in vivo. The developed formulation consisted of an oil-in-water microemulsion stabilized by Tween-80. Pig skin was exposed to ablative fractional laser followed by topical application of vismodegib microemulsion for 4 hours. At 4 hours, 2 days, 5 days, and 9 days, we evaluated vismodegib biodistribution in superficial, mid, and deep dermis and plasma (n = 189 measurements) and assessed local skin reactions. Sustained topical delivery of vismodegib was detected in all depths of ablative fractional laser–exposed skin over the course of the study, with peak concentrations found at 5 days and 9 days. The highest vismodegib concentrations reached 1,409.7 μmol/liter in superficial dermis and 62.3 μmol/liter in deep dermis, exceeding steady-state plasma concentrations previously reported for oral administration of vismodegib (5.5–56.0 μmol/liter). Ablative fractional laser increased vismodegib uptake up to 16.6-fold compared with intact skin. Only mild local skin responses to vismodegib were observed, and no vismodegib was detected in plasma. We report sustained topical delivery of vismodegib in vivo at high concentrations with favorable skin tolerability, suggesting a future safer vismodegib treatment.
AB - Oral administration of vismodegib for basal cell carcinoma treatment is limited by significant class-specific systemic side effects. We investigated the approach of combining ablative fractional laser–assisted drug delivery with an extended-release microemulsion formulation of vismodegib to provide efficient cutaneous delivery in vivo. The developed formulation consisted of an oil-in-water microemulsion stabilized by Tween-80. Pig skin was exposed to ablative fractional laser followed by topical application of vismodegib microemulsion for 4 hours. At 4 hours, 2 days, 5 days, and 9 days, we evaluated vismodegib biodistribution in superficial, mid, and deep dermis and plasma (n = 189 measurements) and assessed local skin reactions. Sustained topical delivery of vismodegib was detected in all depths of ablative fractional laser–exposed skin over the course of the study, with peak concentrations found at 5 days and 9 days. The highest vismodegib concentrations reached 1,409.7 μmol/liter in superficial dermis and 62.3 μmol/liter in deep dermis, exceeding steady-state plasma concentrations previously reported for oral administration of vismodegib (5.5–56.0 μmol/liter). Ablative fractional laser increased vismodegib uptake up to 16.6-fold compared with intact skin. Only mild local skin responses to vismodegib were observed, and no vismodegib was detected in plasma. We report sustained topical delivery of vismodegib in vivo at high concentrations with favorable skin tolerability, suggesting a future safer vismodegib treatment.
U2 - 10.1016/j.jid.2020.01.032
DO - 10.1016/j.jid.2020.01.032
M3 - Journal article
C2 - 32135181
AN - SCOPUS:85082857696
VL - 140
SP - 2051
EP - 2059
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 10
ER -
ID: 260600010