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

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 doxycyclineimprinted 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.

Molecular Dynamics in the Study and Development of Molecularly Imprinted Materials – Status Quo, Quo Vadis?

“…Several studies with the aim to explain the molecular basis of recognition have demonstrated the significance of including all the polymer building blocks in the simulation by illuminating the nature of complex formation and underlying mechanisms [53,54,[160][161][162][163][164][165][166][167][168][169]. Some strategies involved the evaluation of the choice of suitable polymer components such as the type of functional monomer, crosslinker, template or porogen [170][171][172][173][174][175][176] and/or the investigation of the relative stoichiometries between the monomers [172,[175][176][177][178][179][180][181][182][183][184][185][186][187][188] suitable for use in imprinting protocols. A recent example by Rebelo et al [183] reported the development of a MIP-based electrochemical sensor, comprised of a carbon paste electrode modified with MIP microparticles and multi-walled carbon nanotubes, for detection of the antibiotic furazolidone in environmental waters.…”

Pectin–Zeolite-Based Wound Dressings with Controlled Albumin Release

“…Hydrogel systems have been broadly used in the development of delivery systems for drugs [17,18] and protein [19]. Because of their hydrophilic structure [10], natural polysaccharides in hydrogel form such as chitosan [6,20,21], alginate [10,22], starch [23], hyaluronic acid, and pectin [24] have been widely used in the fabrication of dressings for burned, exuding, and bleeding wounds.…”