Enhanced biodistribution and efficacy of nicomenthyl encapsulated in emulsions stabilized by methacrylated hyaluronic acid for the prevention and treatment of skin photoaging.

Nicomenthyl (NM), prodrug of niacinamide (vitamin B3), is widely used in skin applications for their biological benefits, but remain mainly in the stratum corneum (SC). Bioactive methacrylate-functionalized hyaluronic acid (HA-MA) (44.5 KDa; degree of substitution: 80-100%), used to stabilize Oil-in-Water emulsions (EM) as new application for polysaccharide, represent an effective strategy to trespass SC. Here, 265 nm stable EMs containing 5 wt% NM (EM-NM) resulted in 3.22, 2.84 and 1.98 fold-increase of COL I/III and Elastin expression, respectively, compared to basal levels of HDF cells. After 24 h, >90% of HaCat/HDF scratched area was covered with EM-NM, significantly higher than NM alone. UVB protection and anti-inflammatory activity of EM-NM were confirmed by recovering IL-6 basal level for UV-irradiated HaCat/HDF cell. While EM-NM reached stratum basale after 24 h-biodistribution studies, it reduced UVB-induced IL-6/IL-8 expression and restored COL I/III expression in photoaged skin models to healthy skin phenotype. While SPTLC2 expression was increased by 1.87-fold in the epidermis, ELN expression was increased by 1.69-fold in the dermis. Altogether, EM-NM proved to enhance NM biological activity and promote skin barrier function of the epidermis and increase elastin production in the dermis, highlighting its potential as a UV-protective and anti-aging cosmetic ingredient.