Improving nano-particulate carriers for oral drug delivery using archaeal tetraether lipids from novel sources
Mette Sloth Bohsen (PhD fellow sponsored by the PRC) - Department of Biology, University of Southern Denmark, Denmark (firstname.lastname@example.org)
The oral administration of drugs is preferred by patients and the most cost-efficient regarding healthcare personnel. Challenges that are faced with oral administration are premature degradation and poor permeability over the intestinal barrier that especially protein and peptide drugs suffer from, leading to insufficient bioavailability for achieving therapeutically relevant blood/plasma levels. Solutions showing great promise are nanoparticulate drug carriers like phospholipid vesicles (liposomes). However, conventional liposomes lack stability towards the harsh environment of the stomach and intestines. Recently developed advanced liposome formulations employing tetraether lipids (TELs) have shown significant improvements in stability and bioavailability.1) While TELs are present in a range of microorganisms of the domain Archaea, only TELs from two hyperthermophilic species have been tested for oral drug delivery by liposomes so far. Main reasons are the demanding growth requirements of most TEL-producing Archaea, which make the biotechnological production of TELs uneconomical. Yet unexplored sources of TELs are environmental Archaea, mainly Thaumarchaeota, which are abundant in, e.g., wastewater treatment plants and the ocean. They are phylogenetically closely related to hyperthermophilic species and produce unique TELs that have evolved to stabilize the membranes at the ambient temperatures these organisms live at, which is an interesting feature for the use in liposomes.
The aim of the project is to test if environmental sources for TEL-producing Archaea can be exploited in an economical way. For this we will run through the whole process, from biomass collection over lipid extraction and purification, liposome preparation, and testing all the way to bioavailability studies in rats. This will allow us to determine the most promising source for a future large‐scale production of TELs that could supply their commercial use in liposomes for oral drug delivery.
Benefit for the community
The identification of novel, commercially interesting sources to produce tetraether lipids (TELs) will benefit the research community that is developing advanced liposome formulations for oral drug delivery. So far, a reliable, cost-effective supply of TELs is a challenge that hampers the progress in this field of research. If TELs were available for the laboratory to pilot scale production of TEL-containing liposomes, multiple formulations of different peptide and protein drugs could be developed and tested all the way to clinical trials. In the longer run this research will benefit society in general as it will allow for the development of oral formulations of currently hard to administer drugs.
Archaeal Lipids in Oral Delivery of Therapeutic Peptides
Eur. J. Pharm. Sci. 108, 101-110