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, cilt.28, sa.11, 2021 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 28 Sayı: 11
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1007/s10965-021-02740-6
  • Dergi Adı: JOURNAL OF POLYMER RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Chemical Abstracts Core, Communication Abstracts, Compendex, INSPEC, Metadex, Civil Engineering Abstracts
  • Anahtar Kelimeler: Imprinted hydrogel, Molecular simulations, Doxycycline, SOFT CONTACT-LENSES, POLYMER MORPHOLOGY, RATIONAL DESIGN, BINDING-SITES, EYE DROPS, IN-VITRO, RECOGNITION, TEMPLATE, TIMOLOL, DISSOLUTION
  • İstanbul Teknik Üniversitesi Adresli: Evet

Özet

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.