Investigation and preparation of incretin conjugated nanoemulsions as targeted drug delivery systems

Univ.-Prof. Dr. Andreas Zimmer1) – University Graz, Austria

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1.

Univ.-Professor Dr. Andreas ZimmerInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Technology & Biopharmacy Universit├Ątsplatz 1, 8010 Graz, Austria

People involved

B.Sc. Philipp Toplak (master student sponsored by the PRC) - University of Graz, Austria

Abstract

Nanoemulsions (especially o/w nanoemulsions) are a very interesting field in pharmaceutics due to their diverse applications. Besides their application in parenteral nutrition and use as a matrix for lipophilic active pharmaceutical ingredients (APIs), they can be used to modify the pharmacokinetics and the biodistribution of their affiliated drugs, or to prolong the release of a drug in form of a sustained release system, or both. When biodistribution is specifically changed, the term ''targeted drug delivery systems'' is used. Therefore, a ligand/receptor interaction at the cells to be affected and a carrier containing the actual drug substance is required. However, due to stability problems of o/w nanoemulsions and the complexity in analysis of the different production steps their application as pharmaceuticals has been rather challenging.

To promote the use of targeted drug delivery systems, it would be of great advantage to develop a universal synthesis scheme to produce stable, ligand-coupled (e.g. peptide-coupled) o/w nanoemulsions. However, by now research is focusing either on the PEGylation of peptides with varying PEG chain lengths and with molecular weights ranging from 5-50 kDa, or the use of o/w nanoemulsions as matrices for lipophilic drug substances.

This project is about the production of stable o/w nanoemulsions using different egg-lecithins in order to find the most suitable one for this approach, the synthesis of long-acting DSPE-PEG(2000) Maleimide-coupled peptides, and the combination of both. Furthermore, each synthesis step is analyzed with different analytical methods (HPLC, SEC, NMR, MALDI-TOF, laser diffraction, dynamic light scattering, zeta potential) to document the changes in the molecules and drug delivery systems. To demonstrate the functionality of the targeted drug delivery system, cell studies using 3T3-L1 pre-adipocytes will be performed. This knowledge will thus be of great interest, e.g., to the pharmaceutical industry and pharmaceutical scientists as inspiration for novel synthetic strategies and the development of various targeted drug delivery systems using peptide-coupled o/w nanoemulsions.

Benefit for the community

With the help of this project, lipophilic and/or lipophilized active pharmaceutical ingredients could be incorporated into the oil droplets of the o/w nanoemulsions and then released directly into the desired tissue by targeted drug delivery. For example, the lipophilized uncoupling protein 3 (UCP3), which intervenes in the lipid metabolism, could be used for targeted action on adipocytes. While the systemic administration of UCP3 sometimes leads to severe side effects in areas of the body other than the adipocytes, adverse reactions could be reduced or prevented by peptide-coupled drug targeting.

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