Skin penetration of active folate salts and their effects on wound healing in vitro: new approaches for dermal folate application

The skin has a high demand for folates because of its constant renewal and growth. Folates play an important role in the metabolism of healthy skin and in the regeneration of irritated or injured skin. The high proliferation rate supports wound healing in chronic and degenerative skin diseases. In contrast to systemic folate administration, there is little known on skin penetration of folates after topical application. Therefore, skin penetration with L-formyltetrahydrofolate di-arginine salt (L-FTHF-di-arginine), L-formyltetrahydrofolate calcium gluconate mixture (L-FTHF-Ca) and L-methyltetrahydrofolate dicholine salt (L-MTHF-dicholine) was studied. We investigated the epidermal penetration of 2.5% aqueous solution of L-FTHF di-arginine, L-FTHF Ca and L-MTHF dicholine using in vitro reconstructed epidermal skin models. In order to assess an effect on wound healing in vitro, the selected folates were tested in a keratinocyte scratch assay. Analysis of the examined folates in the cell culture medium located opposite of the application site showed their penetration through the reconstructed epidermal model. In epidermal models to which L-FTHF di-arginine was added, L-MTHF dicholine was detected on the opposite site. L-FTHF salts were partially converted to L-MTHF. Improved wound healing was shown in keratinocyte scratch assay when the selected folates were added to the medium.

Dressler D, Engelhart-Jentzsch K, Lambert C

hb TIMES Schw Aerztej. 2023 March 30; 8(1):62-69. doi:10.36000/hbT.2023.09.002