Incorporation of α‐tocopherol in marine lipid‐based liposomes: in vitro and in vivo studies

Abstract

Liposomes made from a natural marine lipid extract and containing a high polyunsaturated n-3 fatty lipid ratio were envisaged as oral route vectors and a potential alpha-tocopherol supplement. The behavior of vesicles obtained by simple filtration and of giant vesicles prepared by electroformation was investigated in gastrointestinal-like conditions. The influence of alpha-tocopherol incorporation into liposomes was studied on both physical and chemical membrane stability. Propanal, as an oxidation product of n-3 polyunsaturated fatty acids, was quantified by static headspace gas chromatography when alpha-tocopherol incorporation into liposome ratios ranged from 0.01 to 12 mol%. Best oxidative stability was obtained for liposomes that contained 5 mol% alpha-tocopherol. Compared to the other formulas, propanal formation was reduced, and time of the oxidation induction phase was longer. Moreover, alpha-tocopherol induced both liposome structural modifications, evidenced by turbidity, and phospholipid chemical hydrolysis, quantified as the amount of lysophospholipids. This physicochemical liposome instability was even more pronounced in acid storage conditions, i.e., alpha-tocopherol incorporation into liposome membranes accelerated the structural rearrangements and increased the rate of phospholipid hydrolysis. In particular, giant vesicles incubated at pH 1.5 underwent complex irreversible shape transformations including invaginations. In parallel, the absorption rate of alpha-tocopherol was measured in lymph-cannulated rats when alpha-tocopherol was administrated, as liposome suspension or added to sardine oil, through a gastrostomy tube. Alpha-tocopherol recovery in lymph was increased by almost threefold, following liposome administration. This may be related to phospholipids that should favor alpha-tocopherol solubilization and to liposome instability in the case of a high amount of alpha-tocopherol in the membranes. A need to correlate results obtained from in vitro liposome behavior with in vivo lipid absorption was demonstrated by this study.

Spectroscopic studies of D-α-tocopherol concentration-induced transformation in egg phosphatidylcholne vesicles

“…There are reports showing that the presence of tocopherol in a suspension of cells promotes fusion [4,5]. In model studies with DPPC and DPMC membranes, it has been shown that the presence of tocopherol in the membrane stabilizes its structure [6,7] via the formation of complexes with membrane lipids [8][9][10]. The tocopherol concentration in the above-described experiments was usually between 2 and 8 mol%, and never higher than 12 mol%.…”

Feeding rats with liposomes or fish oil differently affects their lipid metabolism

“…Fish oil was supplemented with cholesterol (Sigma France, Saint Quentin Fallavier, France) to match the lipid composition of the crude marine lipid mixture used for liposome preparation. Liposomes (100 mg/mL) were prepared as described in the references [29,30]. The suspension consisted of a mixture of spherical vesicles with a variable number of lamellae, characterized by a mean diameter of about 4 mm.…”

“…The esterification of EPA and DHA mainly in the sn-2 position of PL, associated with the supra-molecular organization of the lipids in bilayer structures ensured an oxidative stability of the PUFA and a preformed interface for phospholipase A 2 [27,28]. When marine lipid-based liposomes were tested as active compound delivery systems, it was demonstrated that liposomes favored a-tocopherol [29] and n-3 PUFA [30] bioavailability. Moreover, chylomicron TAG analysis showed that n-3 PUFA molecular distribution depended on the dietary PUFA source [30].…”

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“…It is essential for integrity and optimal function of reproductive, muscular, circulatory, nervous and immune systems (Hoekstra, 1975;Sheffy and Schult z, 1979;McDo well, 2000). The most important determinant of vitamin E requirements is the dietary concentration of unsaturated fatty acids as PUFA are highly susceptible to auto-oxidation (Nacka al et al, 2001). Animals ingesting high levels of PUFA require high concentrations of vitamin E to protect tissue lip ids fro m free radical attack (Debier et al, 2002;Lammi-Keefe and Jensen, 1984;Machlin, 1991).…”