TY - JOUR
T1 - Preformulation evaluation of selumetinib for topical application
T2 - skin distribution and photodegradation analysis using MALDI imaging and LC-MS/MS
AU - Nicol, Edith
AU - Do, Bernard
AU - Vignes, Marina
AU - Annereau, Maxime
AU - Paul, Muriel
AU - Wolkenstein, Pierre
AU - Touboul, David
AU - Secretan, Philippe Henri
N1 - Publisher Copyright:
© 2024 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Understanding drug behavior within the skin, especially for photosensitive compounds, is crucial for developing effective and safe topical therapies. This study employs Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) and Liquid Chromatography-Mass Spectrometry (LC-MS/MS) to investigate the skin permeation and photostability of selumetinib, a MEK inhibitor used in treating type 1 neurofibromatosis (NF1). The highest amounts of selumetinib in the skin sections were obtained when using the gel formulation, suggesting that it is to be preferred to cream formulations to achieve higher permeation of the drug. Our study also revealed that selumetinib is amenable to photodegradation in ex vivo skin explants, and yields one main degradation product, whose degradation is likely triggered by hydrogen abstraction. MALDI-MSI results showed selumetinib and its degradation product concentrate in skin appendages, indicating these structures might serve as drug reservoirs, potentially prolonging retention and efficacy. This study demonstrates that combining MALDI-MSI with LC/MS-MS can highly contribute to the characterization of the fate of photosensitive compounds in the skin, an essential prerequisite to the development of compound-specific photoprotective measures. It will also pave the way for innovative topical delivery strategies for NF1 treatment.
AB - Understanding drug behavior within the skin, especially for photosensitive compounds, is crucial for developing effective and safe topical therapies. This study employs Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) and Liquid Chromatography-Mass Spectrometry (LC-MS/MS) to investigate the skin permeation and photostability of selumetinib, a MEK inhibitor used in treating type 1 neurofibromatosis (NF1). The highest amounts of selumetinib in the skin sections were obtained when using the gel formulation, suggesting that it is to be preferred to cream formulations to achieve higher permeation of the drug. Our study also revealed that selumetinib is amenable to photodegradation in ex vivo skin explants, and yields one main degradation product, whose degradation is likely triggered by hydrogen abstraction. MALDI-MSI results showed selumetinib and its degradation product concentrate in skin appendages, indicating these structures might serve as drug reservoirs, potentially prolonging retention and efficacy. This study demonstrates that combining MALDI-MSI with LC/MS-MS can highly contribute to the characterization of the fate of photosensitive compounds in the skin, an essential prerequisite to the development of compound-specific photoprotective measures. It will also pave the way for innovative topical delivery strategies for NF1 treatment.
KW - MALDI-MS imaging
KW - photodegradation
KW - preformulation
KW - Selumetinib
KW - skin permeation
KW - topical
UR - http://www.scopus.com/inward/record.url?scp=85204434260&partnerID=8YFLogxK
U2 - 10.1080/10837450.2024.2405829
DO - 10.1080/10837450.2024.2405829
M3 - Article
C2 - 39286857
AN - SCOPUS:85204434260
SN - 1083-7450
VL - 29
SP - 855
EP - 861
JO - Pharmaceutical Development and Technology
JF - Pharmaceutical Development and Technology
IS - 8
ER -