In vitro behavior of marine lipid-based liposomes, influence of pH, temperature, bile salts, and phospholipase A(2)

To deliver polyunsaturated fatty acids (PUFA) by the oral route, liposomes based on a natural mixture of marine lipids were prepared by filtration and characterized in media that mimic gastrointestinal fluids. First the influ ence of large pH variations from 1.5-2.5 (stomach) to 7.4 (intestine) at th e physiological temperature (37 degreesC) was investigated. Acidification o f liposome suspensions induced instantaneous Vesicle aggregation, which was partially reversible when the external medium was further neutralized. Sim ultaneously, complex morphological bilayer rearrangements occurred, leading to the formation of small aggregates. These pH- and temperature-dependent structural changes were interpreted in terms of osmotic shock and lipid che mical alterations, i.e., oxidation and hydrolysis, especially in the first hours of storage. Besides, oxidative stability was closely related to the s tate of liposome aggregation and the supramolecular organization (vesicles or mixed micelles). The effects of bile salts and phospholipase A(2) (PLA(2 )) on the liposome structures were also studied. Membrane solubilization by bile salts was favored by preliminary liposome incubation in acid conditio ns. PLA(2) showed a better activity on liposome structures than on the corr esponding mixed lipid-bile salt micelles. As a whole, in spite of slight mo rphological modifications, vesicle structures were preserved after an acid stress and no lipid oxidation products were detected during the first 5 h o f incubation. Thus, marine lipids constituted an attractive material for th e development of liposomes as potential oral PUFA supplements.