New Vitamin D3-based Substances for Topical Treatment of Psoriasis

摘要

A conjugation between polyunsaturated fatty acids (PUFAs) and calcipotriol, a vitamin D3 analog, has produced complexes capable of enhancing penetration into the skin and demonstrated additive anti-proliferative activity in cultured keratinocytes. In vitro and in vivo penetration studies revealed that the conjugates penetrated and distributed the skin in much more efficacious manner than the calcipotriol alone. Comparison between the n-3 and n-6 PUFAs has shown that the significant activity is unique to the n-3 fatty acids. Penetration studies, compared between n-3 and n-6 PUFA demonstrated clear preference to the n- 3 fatty acid. HPLC analysis has shown that after permeation into skin, the conjugate was first converted into another stable isomer form, presumably by transesterification, and only then was hydrolyzed to form high local concentrations of calcipotriol and PUFA.