Elucidating doxycycline loading and release performance of imprinted hydrogels with different cross-linker concentrations: a computational and experimental study


Inan T., Dalgakıran D., Kurkcuoglu O., Güner F. S.

JOURNAL OF POLYMER RESEARCH, vol.28, no.11, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 28 Issue: 11
  • Publication Date: 2021
  • Doi Number: 10.1007/s10965-021-02740-6
  • Journal Name: JOURNAL OF POLYMER RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Chemical Abstracts Core, Communication Abstracts, Compendex, INSPEC, Metadex, Civil Engineering Abstracts
  • Keywords: Imprinted hydrogel, Molecular simulations, Doxycycline, SOFT CONTACT-LENSES, POLYMER MORPHOLOGY, RATIONAL DESIGN, BINDING-SITES, EYE DROPS, IN-VITRO, RECOGNITION, TEMPLATE, TIMOLOL, DISSOLUTION
  • Istanbul Technical University Affiliated: Yes

Abstract

Effective non-covalent molecular imprinting on a polymer depends on the extent of non-bonded interactions between the template and other molecules before polymerization. Here, we first determine functional monomers that can yield a doxycycline-imprinted hydrogel based on the hydrogen bond interactions at the prepolymerization step, revealed by molecular dynamics (MD) simulations, molecular docking, and simulated annealing methods. Then, acrylic acid (AA)-based doxycycline (DOX) imprinted (MIP) and non-imprinted (NIP) hydrogels are synthesized in cross-linker ethylene glycol dimethacrylate (EGDMA) ratios of 1.0, 1.5, 2.0, and 3.0 mol%. Here, molecularly imprinted polymer with 3.0 mol% EGDMA has the highest imprinting factor (1.58) and best controlled drug release performance. At this point, full-atom MD simulations of DOX-AA solutions at different EGDMA concentrations reveal that AA and EGDMA compete to interact with DOX. However, at 3.0 mol% EGDMA, AA attains numerous stable hydrogen bond interactions with the drug. This study demonstrates that the concentration of the cross-linker and functional monomer can be adjusted to increase the success of imprinting, where the interplay between these two parameters can be successfully revealed by MD simulations.