Liposomes containing lipids from Sulfolobus islandicus withstand intestinal bile salts: An approach for oral drug delivery?

Abstract

In an attempt to design an oral drug delivery system, suited to protect labile drug compounds like peptides and proteins against the harsh environment in the stomach and upper intestine, we have prepared liposomes from phospholipids, cholesterol and archaeal lipids. As source for the archaeal lipids we used Sulfolobus islandicus, a hyperthermophilic archaeon, whose lipids have not been used in liposomes before. Culturing conditions and extraction protocols for its membrane lipids were established and the lipid composition of the crude lipid extract was characterized. The extracted membrane lipid fraction of S. islandicus consisted primarily of diether lipids with only a small fraction of tetraether lipids. Small unilamellar liposomes with 18% (mol/mol) of crude archaeal lipid extract were from S. islandicus were produced, for the first time and proven to be stabilized against aggressive bile salts as determined by loss of entrapped marker (calcein). At 4.4mM taurocholate (physiological taurocholate level) liposomes containing archaeal lipids retained entrapped marker better than liposomes made of egg phosphatidylcholine (PC) alone and to an extent similar to liposomes made of egg PC and cholesterol. Our findings showed that crude archaeal lipid extracts have, to a certain extent, stabilizing effects on liposomes similar to purified tetraether lipid fractions tested previously.