Oral Peptide Delivery: Design of Peptide/Lipid Complexes

Due to the great progress in biotechnology industry is capable of producing a large number of potential therapeutic peptides in commercial quantities. Most of these drugs, however, have to be administered parenterally although the oral route would be highly favored. Within recent years lipophilic delivery systems such as self-emulsifying drug delivery systems (SEDDS) turned out to be a promising strategy for oral peptide delivery. Although various oral lipophilic peptide delivery systems are already in phase 2 and 3 clinical trials, this technology has by far not reached its full potential. The likely greatest constraint is the poor incorporation of peptides in the lipophilic phase of such delivery systems. This project focuses therefore on the design and characterization of novel more efficient peptide/lipid complexes (=PELIPs). In particular it is the aim of this project: o to identify the most essential types of interactions between peptides and lipids in order to form more potent PELIPs o to identify the most suitable combinations of lipids for complexes that can more efficiently overcome cell membranes o to investigate their fate on the way across the absorption barrier and in the systemic circulation o to evaluate the impact of PELIPs release from SEDDS and the impact of PELIPs stability on their oral bioavailability Starting with in silico analyses on peptide lipid interactions and based on already available know-how a great variety of PELIPs is generated. Those exhibiting the highest lipophilic character (I), the highest efficacy to permeate cell membranes (II) and the highest safety profile (III) are incorporated in SEDDS and their potential for oral peptide delivery is evaluated in vivo. Moreover, the fate of PELIPs on their way from the GI-tract in the systemic circulation is investigated in detail and compared with the efficacy of corresponding free not complexed peptide/lipid mixtures. The project will provide substantial information about mechanisms being responsible for the uptake of peptides from mucosal membranes via lipophilic complexes. It will essentially contribute to more efficient oral peptide drug delivery systems.

Because of the fast progress in biotechnology a huge number of therapeutic peptides is registered as new medicines. These products, however, have to be administered via injections, that are strongy limiting their compliance. Within this project lipid-based nanocarrier systems were developed, that enable the oral administration of these drugs. In particular self-emulsifying drug delivery systems (SEDDS), in that various therapeutic peptides were incorporated by hydrophobic ion pairing, showed an oral bioavailability of up to 30%. Based on these results therapeutic peptides can be administered in form of tablets or capsules.