Encapsulation and targeted transport of compounds

Enzymes and “helper proteins” of lipid mediator biosynthesis represent important drug targets for the treatment of inflammatory diseases, for some of which no drugs have yet been approved in Europe. Our goal is the development and molecular pharmacological evaluation of dual or multiple inhibitors that target 5-lipoxygenase, 5-lipoxygenase-activating protein (FLAP), leukotriene C4 synthase, microsomal prostaglandin E₂ synthase (mPGES)-1 and/or inhibit soluble epoxide hydrolase. The design, synthesis and computer-aided analysis of the compounds is carried out in close collaboration with external partners. Many of these active ingredients are highly lipophilic, which has an unfavorable effect on the pharmacokinetic properties. In cooperation with working groups in pharmaceutical technology we are encapsulating these substances as well as previously tested natural products and their derivatives (indirubins, boswellic acids, etc.) into polymer-based nanoparticles in order to improve bioavailability, achieve targeted transport to the site of inflammation, and the absorption and release of the active ingredients within innate immune cells (monocytes, macrophages, neutrophils).

Key publications:

Pein H., Ville A., Pace S., Temml V., Garscha U., Raasch M., Alsabil K., Viault G., Dinh C-P.,  Guilet D., Troisi F., Neukirch K., König S., Bilancia R., Waltenberger B., Stuppner H., Wallert M., Lorkowski S., Weinigel C., Rummler S., Birringer M., Roviezzo F., Sautebin L., Helesbeux J.-J., Séraphin D., Mosig A., Schuster D., Rossi A., Richomme P., Werz O.*, Koeberle A.* (2018) Endogenous metabolites of vitamin E limit inflammation by targeting 5 lipoxygenase. Nat Commun, 9, 3834

Czapka A., Grune C., Schädel P., Bachmann V., Scheuer K., Dirauf M., Weber C., Skaltsounis A., Jandt K.D., Schubert U.S., Fischer D., Werz O. (2022) Drug delivery of 6-bromoindirubin-3’-glycerol-oxime ether employing poly(D,L-lactide-co-glycolide)-based nanoencapsulation techniques with sustainable solvents. J Nanobiotechnology, 20(1):5

Kretzer C., Shkodra B., Klemm P., Jordan P.M., Schröder D., Cinar G., Vollrath A., Schubert S., Nischang I., Hoeppener S., Stumpf S., Banoglu E., Gladigau F., Bilancia R., Rossi A., Eggeling C., Neugebauer U., Schubert U.S., Werz O. (2021) Ethoxy acetalated dextran-based nanocarriers accomplish efficient inhibition of leukotriene formation by a novel FLAP antagonist in human leukocytes and blood. Cell Mol Life Sci, 79(1):40

Collaborative Research Center: 

DFG SFB1278 „Polytarget“