Nanoparticles with a combination of lipophilic and hydrophilic drugs Silke Notter, a Dolma Choezom, b Frauke Alves b and Claus Feldmann* ,a a Institute for Inorganic Chemistry, Karlsruher Institute of Technology, Engesserstr. 15, 76131 Karlsruhe, Germany b Institute for Diagnostic and Interventional Radiology, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany Drug resistance is a major challenge for chemotherapy. Especially, this holds for metastases that emerge after the initial treatment of the primary tumour. A so-called combination therapy is often used to treat resistant cells through simultaneously administration of a cocktail of drugs. Herein, a simultaneous uptake of the drugs is not guaranteed due to the different distribution behaviour in the body. Moreover, freely dissolved and distributed drugs cause a range of severe side effects. The use of drug delivery systems like nanoparticles promises a local and simultaneous uptake through a targeted release with a reduction of side effects. [1] Thus, we aim at combining the advantages of combination therapy with those of nanoparticles to develop nanoparticle-based systems to specifically address resistant cells and side effects. The combination of lipophilic and hydrophilic drugs is particular interesting since this addresses different mechanisms of action, which can lead to strong synergistic effects. The synthetic difficulty of combining high loads of both lipophilic and hydrophilic drugs in a single particle explains the current lack of such systems in literature. However, with our three-step synthesis route based on a solvent-antisolvent-synthesis, core@shell nanoparticles with a lipophilic drug core and a hydrophilic drug shell are accessible. [2,3] References 1. D. Rudolph, N. Redinger, U. E. Schaible, C. Feldmann, ChemNanoMat 2020, 7 , 7. 2. J. Napp, F. Alves, D. Rudolph, C. Feldmann, Patent application , EP21212525.6. 3. D. Rudolph, N. Redinger, K. Schwarz, F. Li, G. Hädrich, M. Cohrs, L. A. Dailey, U. E. Schaible, C. Feldmann, ACS Nano , 2023, in press .
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