title: Thermodynamic compatibility of actives encapsulated into PEG-PLA nanoparticles: In Silico predictions and experimental verification.
abstract: Achieving optimal solubility of active substances in polymeric carriers is of fundamental importance for a number of industrial applications, including targeted drug delivery within the growing field of nanomedicine. However, its experimental optimization using a trial-and-error approach is cumbersome and time-consuming. Here, an approach based on molecular dynamics (MD) simulations and the Flory-Huggins theory is proposed for rapid prediction of thermodynamic compatibility between active species and copolymers comprising hydrophilic and hydrophobic segments. In contrast to similar methods, our approach offers high computational efficiency by employing MD simulations that avoid explicit consideration of the actual copolymer chains. The accuracy of the method is demonstrated for compatibility predictions between pyrene and nile red as model dyes as well as indomethacin as model drug and copolymers containing blocks of poly(ethylene glycol) and poly(lactic acid) in different ratios. The results of the simulations are directly verified by comparison with the observed encapsulation efficiency of nanoparticles prepared by nanoprecipitation. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Otto Schott Institute of Materials Research (OSIM), Friedrich Schiller University Jena, Löbdergraben 32, Jena, 07743, Germany.|Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, Jena, 07743, Germany.
authors.forename: Andreas
authors.identifier: 0000-0003-3261-6443
authors.initials: A
authors.lastname: Erlebach
authors.affiliation: Otto Schott Institute of Materials Research (OSIM), Friedrich Schiller University Jena, Löbdergraben 32, Jena, 07743, Germany.
authors.forename: Timm
authors.initials: T
authors.lastname: Ott
authors.affiliation: Otto Schott Institute of Materials Research (OSIM), Friedrich Schiller University Jena, Löbdergraben 32, Jena, 07743, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Otzen
authors.affiliation: Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, Jena, 07743, Germany.|Department of Pharmaceutical Technology, Institute of Pharmacy, Friedrich Schiller University Jena, Otto-Schott-Str. 41, Jena, 07745, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schubert
authors.affiliation: Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, Jena, 07743, Germany.|Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, Jena, 07743, Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Czaplewska
authors.affiliation: Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, Jena, 07743, Germany.|Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, Jena, 07743, Germany.
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Schubert
authors.affiliation: Otto Schott Institute of Materials Research (OSIM), Friedrich Schiller University Jena, Löbdergraben 32, Jena, 07743, Germany.|Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, Jena, 07743, Germany.
authors.forename: Marek
authors.initials: M
authors.lastname: Sierka
keywords: Flory-Huggins theory; atomistic simulations; molecular dynamics; polymeric nanoparticles