THE EFFICIENCY OF ANTIOXIDANTS DELIVERED BY LIPOSOMAL TRANSFER

Phenolic antioxidants of the hydroxychroman class, alpha-tocopherol (a lpha-TOC) and 2,2,5,6,7-pentamethyl-6-hydroxychroman (PMHC), and the h indered phenols ihydro-5-hydroxy-2,2,4-trimethylnaphto[1,2-b]furan (NF UR), 2,6-di-tert-butyl-4-methoxyphenol (DBHA), and 2,6-di-tert-butyl-4 -methyl phenol (BHT), were delivered into oxidizable (ACCEPTOR) liposo mes of dilinoleoylphosphatidylcholine (DLPC) or 1-palmitoyl-2-linoleoy l-phosphatidylcholine (PLPC) from saturated DONOR liposomes of dimyris toylphosphalidylcholine (DMPC) by liposomal transfer. The antioxidant activities, k(inh), by the inhibited oxygen uptake method were compare d with the k(inh)(S) determined whtn the oxidants were introduced into the liposomes by coevaporation from organic solvents. The peroxidatio ns were initiated using either thermal initiators, water-soluble azo-b is-amidinopropane hydrochloride (ABAP), lipid-soluble azo-bis-2,4-dime thylvaleronitrile (ADVN) and di-tert-butylhyponitrite (DBHN), or the p hotoinitiator benzophenone. The antioxidants PMHC, NFUR, DBHA, and BHT transferred rapidly between liposomes, but several hours of incubatio n were needed to transfer alpha-TOC. The average k(inh)(S) in liposome s, in the relative order NFUR 2 DBHA > PMHC > BHT similar or equal to alpha-TOC, were markedly lower than known values in organic solvent. k (inh) values in liposomes appear to be controlled by effects of hydrog en bonding with water and by restricted diffusion of antioxidants, esp ecially in the case of alpha-TOC. Product studies of the hydroperoxide s formed during inhibited oxygen consumption were carried out. The cis ,trans/trans,trans (c,t/t,t) product ratios of the 9- and 13-hydropero xides formed from PLPC during inhibited peroxidation by PMHC were simi lar for both the coevaporated and liposomal transfer procedures. The c ,t/t,t ratio for the same concentration of alpha-TOC, 1.52, compares t o a value of 1.69 for PMHC at the start of the inhibition period. The higher c,t/t,t ratio observed for NFUR in DLPC, which varied between v alues of 7.0 at the start of the inhibition to about 1.8 after the bre ak in the induction period, is a reflection of the increased hydrogen atom donating ability of the antioxidant plus the increased concentrat ion of oxidizable lipid provided by DLPC. (C) 1997 Elsevier Science B. V.