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Tony Bewersdorff,1 Alexandra Gruber,2 Murat Eravci,1 Malti Dumbani,1 Daniel Klinger,2 Andrea Haase1 1German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin, Germany; 2Freie Universität Berlin, Institute of Pharmacy (Pharmaceutical Chemistry), Berlin, GermanyCorrespondence: Andrea HaaseGerman Federal Institute for Risk Assessment, Department of Chemical and Product Safety, Max-Dohrn-Strasse 8–10, Berlin 10589, GermanyTel +49 30 184 122 7600Email Andrea.Haase@bfr.bund.deDaniel KlingerFreie Universität Berlin, Institute of Pharmacy (Pharmaceutical Chemistry), Königin-Luise Street 2-4, Berlin 14195, GermanyTel +49 308 386 0001Email Daniel.Klinger@fu-berlin.deBackground and purpose: Nanogels (NGs) are promising drug delivery tools but are typically limited to hydrophilic drugs. Many potential new drugs are hydrophobic. Our study systematically investigates amphiphilic NGs with varying hydrophobicity, but similar colloidal features to ensure comparability. The amphiphilic NGs used in this experiment consist of a hydrophilic polymer network with randomly distributed hydrophobic groups. For the synthesis we used a new synthetic platform approach. Their amphiphilic character allows the encapsulation of hydrophobic drugs. Importantly, the hydrophilic/hydrophobic balance determines drug loading and biological interactions. In particular, protein adsorption to NG surfaces is dependent on hydrophobicity and critically determines circulation time. Our study investigates how network hydrophobicity influences protein binding, biocompatibility and cellular uptake.Methods: Biocompatibility of the NGs was examined by WST-1 assay in monocytic-like THP-1 cells. Serum protein corona formation was investigated using dynamic light scattering and two-dimensional gel electrophoresis. Proteins were identified by liquid chromatography-tandem mass spectrometry. In addition, cellular uptake was analyzed via flow cytometry.Results: All NGs were highly biocompatible. The protein binding patterns for the two most hydrophobic NGs were very similar to each other but clearly different from the hydrophilic ones. Overall, protein binding was increased with increasing hydrophobicity, resulting in increased cellular uptake.Conclusion: Our study supports the establishment of structure–property relationships and contributes to the accurate balance between maximum loading capacity with low protein binding, optimal biological half-life and good biocompatibility. This is an important step to derive design principles of amphiphilic NGs to be applied as drug delivery vehicles.Keywords: adjustable amphiphilic nanogels, tuneable hydrophilic/hydrophobic balance, biocompatibility, cellular uptake, protein corona, THP-1 cells |
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