2-o-acyl-3-o-(1-acyloxyalkyl) prodrugs of 5,6-isopropylidene-l-ascorbic acid and l-ascorbic acid: Antioxidant activity and ability to permeate silicone membranes

Abstract

2-O-Acyl-3-O-(1-acyloxyalkyl) prodrug derivatives, 15, of 5,6-isopropylidene-L-ascorbic acid, VCA, and L-ascorbic acid, VC, have been characterized by measuring (1) their solubilities in water (SAQ) and in 1-octanol (SOCT); (2) the ability of one member of the homologous series, 15a, to diffuse through a silicone membrane from its application in propylene glycol:water (PG:AQ), 30:70; (3) the ability of another member of the series, 15e, to express cellular antioxidant activity (CAA) in HaCaT cells; and (4) the ability of 15e to support cell viability in HaCaT cells. All of the prodrugs were more soluble in 1-octanol than VC or VCA were. 15a, which exhibited a good balance betweenSOCT andSAQ, was found to deliver approximately 15 times more 15a than VCA delivered VCA through a silicone membrane from PG:AQ, 30:70. Under those conditions, no VC permeated the membrane. 15e, which hydrolyzed to release acetaldehyde as a byproduct instead of the toxin formaldehyde, exhibited approximately 30 times the antioxidant activity of VC in CaHaT cells and supported cell viability up to 900 μM in HaCaT cells.