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Characterization of Electrospun Polysuccinimide-Dopamine Conjugates and Effect on Cell Viability and Uptake
Authors:Krisztina Tóth  Krisztina S Nagy  Zeliha Güler  Ákos György Juhász  Éva Pállinger  Gábor Varga  A Sezai Sarac  Miklós Zrínyi  Angéla Jedlovszky-Hajdú  Dávid Juriga
Institution:1. Laboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089 Hungary;2. Department of Nanoscience and Nanoengineering, Istanbul Technical University, Istanbul, 34469 Turkey

Department of Obstetrics and Gynecology, Amsterdam Reproduction and Development, Amsterdam UMC, location AMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ the Netherlands;3. Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089 Hungary;4. Department of Oral Biology, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089 Hungary;5. Department of Nanoscience and Nanoengineering, Istanbul Technical University, Istanbul, 34469 Turkey

Abstract:Biocompatible nanofibrous systems made by electrospinning have been studied widely for pharmaceutical applications since they have a high specific surface and the capability to make the entrapped drug molecule amorphous, which increases bioavailability. By covalently conjugating drugs onto polymers, the degradation of the drug as well as the fast clearance from the circulation can be avoided. Although covalent polymer–drug conjugates have a lot of advantages, there is a lack of research focusing on their nano-formulation by electrospinning. In this study, polysuccinimide (PSI) based electrospun fibrous meshes conjugated with dopamine (DA) are prepared. Fiber diameter, mechanical properties, dissolution kinetics and membrane permeability are thoroughly investigated, as these are crucial for drug delivery and implantation. Dopamine release kinetics prove the prolonged release that influenced the viability and morphology of periodontal ligament stem cells (PDLSCs) and SH-SY5Y cells. The presence of dopamine receptors on both cell types is also demonstrated and the uptake of the conjugates is measured. According to flow cytometry analysis, the conjugates are internalized by both cell types, which is influenced by the chemical structure and physical properties. In conclusion, electrospinning of PSI-DA conjugates alters release kinetics, meanwhile, conjugated dopamine can play a key role in cellular uptake.
Keywords:cellular uptake  dopamine  dopamine receptor  electrospinning  polymer–drug conjugate  polysuccinimide  SH-SY5Y
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