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Think Beyond the Core: Impact of the Hydrophilic Corona on Drug Solubilization Using Polymer Micelles.
Haider, Malik Salman; Lübtow, Michael M; Endres, Sebastian; Forster, Stefan; Flegler, Vanessa J; Böttcher, Bettina; Aseyev, Vladimir; Pöppler, Ann-Christin; Luxenhofer, Robert.
Afiliação
  • Haider MS; Functional Polymer Materials, Chair for Chemical Technology of Material Synthesis and Bavarian Polymer Institute, Faculty of Chemistry and Pharmacy, University of Würzburg, Röntgenring 11, 97070 Würzburg, Germany.
  • Lübtow MM; Functional Polymer Materials, Chair for Chemical Technology of Material Synthesis and Bavarian Polymer Institute, Faculty of Chemistry and Pharmacy, University of Würzburg, Röntgenring 11, 97070 Würzburg, Germany.
  • Endres S; Institute of Organic Chemistry, Faculty of Chemistry and Pharmacy, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
  • Forster S; Functional Polymer Materials, Chair for Chemical Technology of Material Synthesis and Bavarian Polymer Institute, Faculty of Chemistry and Pharmacy, University of Würzburg, Röntgenring 11, 97070 Würzburg, Germany.
  • Flegler VJ; Biocenter and Rudolf Virchow Centre, University of Würzburg, Haus D15, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
  • Böttcher B; Biocenter and Rudolf Virchow Centre, University of Würzburg, Haus D15, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
  • Aseyev V; Department of Chemistry, University of Helsinki, PB 55, Helsinki FIN-00014, Finland.
  • Pöppler AC; Institute of Organic Chemistry, Faculty of Chemistry and Pharmacy, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
  • Luxenhofer R; Functional Polymer Materials, Chair for Chemical Technology of Material Synthesis and Bavarian Polymer Institute, Faculty of Chemistry and Pharmacy, University of Würzburg, Röntgenring 11, 97070 Würzburg, Germany.
ACS Appl Mater Interfaces ; 12(22): 24531-24543, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32378873
ABSTRACT
Polymeric micelles are typically characterized as core-shell structures. The hydrophobic core is considered as a depot for hydrophobic molecules, and the corona-forming block acts as a stabilizing and solubilizing interface between the core and aqueous milieu. Tremendous efforts have been made to tune the hydrophobic block to increase the drug loading and stability of micelles, whereas the role of hydrophilic blocks is rarely investigated in this context, with poly(ethylene glycol) (PEG) being the gold standard of hydrophilic polymers. To better understand the role of the hydrophilic corona, a small library of structurally similar A-B-A-type amphiphiles based on poly(2-oxazoline)s and poly(2-oxazine)s is investigated by varying the hydrophilic block A utilizing poly(2-methyl-2-oxazoline) (pMeOx; A) or poly(2-ethyl-2-oxazoline) (pEtOx; A*). In terms of hydrophilicity, both polymers closely resemble PEG. The more hydrophobic block B bears either a poly(2-oxazoline) and poly(2-oxazine) backbone with C3 (propyl) and C4 (butyl) side chains. Surprisingly, major differences in loading capacities from A-B-A > A*-B-A > A*-B-A* is observed for the formulation with two poorly water-soluble compounds, curcumin and paclitaxel, highlighting the importance of the hydrophilic corona of polymer micelles used for drug formulation. The formulations are also characterized by various nuclear magnetic resonance spectroscopy methods, dynamic light scattering, cryogenic transmission electron microscopy, and (micro) differential scanning calorimetry. Our findings suggest that the interaction between the hydrophilic block and the guest molecule should be considered an important, but previously largely ignored, factor for the rational design of polymeric micelles.

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Revista: ACS Appl Mater Interfaces Assunto da revista: Biotecnologia / Engenharia Biomédica Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Alemanha