(PTFS13-02-24) Mimicking Sun Exposure With a Novel Transdermal Vitamin D Supplement: A Focus on Local Keratinocyte and Systemic Production of the Vitamin D Binding Protein

Objectives: Vitamin D (VD) deficiency has been associated with various health disorders, but most clinical trials have failed to demonstrate the benefits of oral VD supplementation. Administering VD via the skin may overcome this problem as the vitamin D binding protein (VDBP) helps to absorb and distribute VD from the cutaneous tissue. This study aimed to better understand transdermal VD supplementation using a new vitamin D phosphate analogue (VDP) through comparison to oral supplementation and sun exposure.

Methods: In vitro metabolism of VDP in the skin and intestinal epithelium were studied using rat epidermal keratinocytes (REK) and human epithelial Caco-2 cells respectively. Cells were treated with 10 µM VDP over 24 h. In vivo absorption of VDP was studied in adult male rats treated with a VDP patch compared to VDP capsules, and in adult female mice treated with a VDP patch compared to a single UVB dose of 1.9 J/cm² (280 – 320 nm). VD and metabolites levels were analysed using GC-MS with a limit of detection of < 10 ng/ml. Skin and blood serum VDBP levels were quantified by a sandwich enzyme-linked immunosorbent assay.

Results: VDP was converted to VD rapidly in both REK and Caco-2 cells, with detectable levels at 1 h, and > 50% dose conversion at 24 h. At least 5% of the VDP dose administered was also found to be converted to the active metabolite, 1,25(OH)2D₃, in the keratinocytes compared to 1.8% by the Caco-2 cells. VDP dosing increased VDBP levels in REK cells, but not in the Caco-2 cells. In vivo VDP skin and oral administration showed a similar 25(OH)D₃ response 72 h after dosing, but only the skin induced a significantly higher local (420.4 ± 48.4 µg/g tissue) (p < 0.01) and circulating level of VDBP (480.4 ± 64.3 µg/ml) (p < 0.001) compared to untreated animals. Preliminary data showed that the transdermal VDP patch and UV exposure produced a similar increase in local (patch 385.9 ± 39.8 µg/g tissue, UV 346.8 ± 3.3 µg/ml) and systemic (patch 520.2 ± 49.7, UV 440.2 ± 43.8 µg/ml) VDBP at 24 h post-dosing compared to control (186.0 ± 24.7 µg/g tissue and 228.8 ± 19.2 µg/ml) (p < 0.01).

Conclusions: Transdermal vitamin D supplementation using VDP was effective and increased VDBP levels akin to UV exposure, which if replicated in humans, could represent an innovative means to address deficiency

Funding Sources: This work was supported by the UKRI BBSRC and Curapel Ltd.