New Vitamin D3-based Substances for Topical Treatment of Psoriasis

摘要

A conjugation between polyunsaturated fattyrnacids (PUFAs) and calcipotriol, a vitamin D3 analog,rnhas produced complexes capable of enhancingrnpenetration into the skin and demonstrated additivernanti-proliferative activity in cultured keratinocytes. Inrnvitro and in vivo penetration studies revealed that thernconjugates penetrated and distributed the skin in muchrnmore efficacious manner than the calcipotriol alone.rnComparison between the n-3 and n-6 PUFAs hasrnshown that the significant activity is unique to the n-3rnfatty acids. Penetration studies, compared between n-3rnand n-6 PUFA demonstrated clear preference to the n-rn3 fatty acid. HPLC analysis has shown that afterrnpermeation into skin, the conjugate was first convertedrninto another stable isomer form, presumably by transesterification,rnand only then was hydrolyzed to formrnhigh local concentrations of calcipotriol and PUFA.