The efficiency of antioxidants delivered by liposomal transfer.
Phenolic antioxidants of the hydroxychroman class, alpha-tocopherol (alpha-TOC) and 2,2,5,6,7-pentamethyl-6-hydroxychroman (PMHC), and the hindered phenols 2,3-dihydro-5-hydroxy-2,2,4-trimethylnaphtho[1,2-b]furan (NFUR), 2,6-di-tert-butyl-4-methoxyphenol (DBHA), and 2,6-di-tert-butyl-4-methyl phenol (BHT), were delivered into oxidizable (ACCEPTOR) liposomes of dilinoleoylphosphatidylcholine (DLPC) or 1-palmitoyl-2-linoleoyl-phosphatidylcholine (PLPC) from saturated DONOR liposomes of dimyristoylphosphatidylcholine (DMPC) by liposomal transfer. The antioxidant activities, k(inh), by the inhibited oxygen uptake method were compared with the k(inh)s determined when the antioxidants were introduced into the liposomes by coevaporation from organic solvents. The peroxidations were initiated using either thermal initiators, water-soluble azo-bis-amidinopropane hydrochloride (ABAP), lipid-soluble azo-bis-2,4-dimethylvaleronitrile (ADVN) and di-tert-butylhyponitrite (DBHN), or the photoinitiator benzophenone. The antioxidants PMHC, NFUR, DBHA, and BHT transferred rapidly between liposomes, but several hours of incubation were needed to transfer alpha-TOC. The average k(inh)s in liposomes, in the relative order NFUR approximately DBHA > PMHC > BHT approximately alpha-TOC, were markedly lower than known values in organic solvent. k(inh) values in liposomes appear to be controlled by effects of hydrogen bonding with water and by restricted diffusion of antioxidants, especially in the case of alpha-TOC. Product studies of the hydroperoxides formed during inhibited oxygen consumption were carried out. The cis,trans/trans,trans (c,t/t,t) product ratios of the 9- and 13-hydroperoxides formed from PLPC during inhibited peroxidation by PMHC were similar for both the coevaporated and liposomal transfer procedures. The c,t/t,t ratio for the same concentration of alpha-TOC, 1.52, compares to 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 values of 7.0 at the start of the inhibition to about 1.8 after the break in the induction period, is a reflection of the increased hydrogen atom donating ability of the antioxidant plus the increased concentration of oxidizable lipid provided by DLPC.
Barclay
L R
LR
Department of Chemistry, Mount Allison University, Sackville, Canada.
Antunes
F
F
Egawa
Y
Y
McAllister
K L
KL
Mukai
K
K
Nishi
T
T
Vinqvist
M R
MR
D000578:Amidines; D000975:Antioxidants / Q000737:chemistry*; D001391:Azo Compounds; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives / Q000737:chemistry; D002839:Chromans / Q000737:chemistry; D004134:Dimyristoylphosphatidylcholine; D005663:Furans / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry*; D008956:Models, Chemical; D009570:Nitriles; D010101:Oxygen Consumption; D010713:Phosphatidylcholines; D014810:Vitamin E / Q000737:chemistry / Q000494:pharmacology
D000578:Amidines; D000975:Antioxidants; D001391:Azo Compounds; D002839:Chromans; D005663:Furans; D008081:Liposomes; D009570:Nitriles; D010713:Phosphatidylcholines; C055792:2,2'-azobis(2,4-dimethylvaleronitrile); D014810:Vitamin E; D002084:Butylated Hydroxytoluene; C010915:2,6-di-tert-butyl-4-hydroxymethylphenol; C002448:1,2-linoleoylphosphatidylcholine; C055402:1-palmitoyl-2-linoleoylphosphatidylcholine; C046728:2,2'-azobis(2-amidinopropane); D004134:Dimyristoylphosphatidylcholine