Permeation and metabolism of a novel ascorbic acid derivative, disodium isostearyl 2-O-L-ascorbyl phosphate, in human living skin equivalent models.
A novel amphiphilic vitamin C (VC) derivative, disodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-2Na), which possesses a C(18) alkyl chain attached to a stable ascorbate derivative, sodium L-ascorbic acid 2-phosphate (VCP-Na), was evaluated as a topical prodrug of VC with transdermal activity in human living skin equivalent (LSE) models. The permeation assay used was EPI-606X in the Franz-type diffusion cell system. VCP-IS-2Na exhibited much better permeability than VC and VCP-Na. The accumulation assays applied were EPI-200X and LSE-high by the dynamic system. The increased skin accumulation of VCP-IS-2Na was superior to that of VCP-Na and VC. VCP-IS-2Na that is susceptible to enzymatic hydrolysis by esterase and/or phosphatase released VC in the skin. Measurement of the metabolites that permeated and accumulated from the skin model suggested that VCP-IS-2Na was mainly metabolized via VCP-Na to VC in EPI-606X and EPI-200X, while it was mainly metabolized directly to VC in TESTSKIN LSE-high. Thus, these characteristics indicate that the novel VC derivative, VCP-IS-2Na, may be advantageous as a readily available source of VC for skin care applications.
Shibayama
H
H
Department of Dermatology, Jichi Medical University, Shimotsuke, Japan. ueb37453@nifty.com
Hisama
M
M
Matsuda
S
S
Ohtsuki
M
M
D000279:Administration, Cutaneous; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012869:Skin Absorption; D014815:Vitamins / Q000008:administration & dosage / Q000493:pharmacokinetics*
D011355:Prodrugs; D014815:Vitamins; C011669:ascorbate-2-phosphate; C528521:disodium isostearyl 2-O-L-ascorbyl phosphate; D001205:Ascorbic Acid