Permeation and metabolism of a series of novel lipophilic ascorbic acid derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids with a branched-acyl chain, in a human living skin equivalent model.
A series of novel lipophilic vitamin C derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids possessing a branched-acyl chain of varying length from C(8) to C(16) (6-bAcyl-AA-2G), were evaluated as topical prodrugs of ascorbic acid (AA) with transdermal activity in a human living skin equivalent model. The permeability of 6-bAcyl-AA-2G was compared with those of the derivatives having a straight-acyl chain (6-sAcyl-AA-2G). Out of 10 derivatives of 6-sAcyl-AA-2G and 6-bAcyl-AA-2G, 6-sDode-AA-2G and 6-bDode-AA-2G exhibited most excellent permeability in this model. Measurement of the metabolites permeated from the skin model suggested that 6-bDode-AA-2G was mainly hydrolyzed via 6-O-acyl AA to AA by tissue enzymes, while 6-sDode-AA-2G was hydrolyzed via 2-O-alpha-D-glucopyranosyl-L-ascorbic acid to AA. The former metabolic pathway seems to be advantageous for a readily available source of AA, because 6-O-acyl AA, as well as AA, is able to show vitamin C activity.
Tai
Akihiro
A
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
Goto
Satomi
S
Ishiguro
Yutaka
Y
Suzuki
Kazuko
K
Nitoda
Teruhiko
T
Yamamoto
Itaru
I
D000215:Acylation; D000287:Administration, Topical; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism*
D001205:Ascorbic Acid