Exploring environmental sources of archaeal lipids for improving liposomes for oral drug delivery

While the oral route of drug administration is very cost efficient and has high patient compliance, challenges that especially modern therapeutic protein and peptide drugs face are, among others, premature degradation and poor permeability over the intestinal barrier. The use of nanoparticulate drug carriers like liposomes (spherical vesicles surrounded by a phospholipid bilayer) is a promising way of overcoming these challenges. Advanced liposome formulations often contain enhancers to further stabilize the lipid bilayer, with archaeal tetraether lipids (TELs) being a fairly recently established enhancer. TELs can be found in hyperthermophilic Crenarchaeota, however their demanding growth requirements make the biotechnological production of TELs so far uneconomical. Yet unexplored sources of TELs are environmental Thaumarchaeota, which can be found in many environments including the ocean, soil, freshwater and also wastewater treatment plants (WWTP). To explore if indeed TELs from Thaumarchaeota can be used as enhancers of liposome stability, we collected biomass from different biological treatments at the Ejby Mølle WWTP (Odense) and subsequently optimized protocols for extracting lipids, settling on a modified Blight & Dyer protocol. These efforts were guided by a screening of the biological treatments of the WWTP for Archaea, indicating the presence of Thaumarchaeota, although often at low abundances. The initial results of these studies will be presented and discussed.