G-quadruplex Hydrogel-based Stimuli-responsive High-internal-phase Emulsion Scaffold for Biocatalytic Cascades and Synergistic Antimicrobial Activity

20 March 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


High internal phase emulsions (HIPEs) are non-equilibrium systems with distorted liquid droplet shapes consisting of high volume of internal phase (>74% v/v), enabling high loading of pharmaceutics and useful viscoelastic properties. Stability of the HIPEs is low and requires a high volume of surfactants in the continuous phase, which is environmentally unfriendly. Utilization of hydrogel as the continuous phase to stabilize HIPEs would offer a robust method to produce stable HIPE gels displaying reconfigurable and biocompatible properties, as well as access the huge repertoire of different biocompatible hydrogels. Herein, we introduce a new gel-immobilized HIPE (HIPEG) using chiral G-quadruplex (GQ) based hydrogel with external stimuli-responsive dual-drug release behavior, which is scarce for HIPEs. The hydrophilic and hydrophobic compartments of HIPEGs allow encapsulation of different drugs in both the compartments, with stimuli-responsive diffusion mediated release. Encapsulation of natural oils and antibiotics produces synergistic antimicrobial effects on both Gram positive (MRSA) and Gram negative (P. aeruginosa) bacterial strains. Moreover, we demonstrate biocatalytic reaction networks utilizing compartmentalized enzyme dyads. Notably, the ideal viscoelastic property of HIPEGs enables 3D bioprinting into different shapes, making the scaffold potential for tissue engineering applications. Altogether, our approach offers a one-step route to stimuli-responsive HIPE microcompartments immobilized in GQ hydrogels with endogenous reactivity and high viscoelasticity, and provides a viable step towards the development of biocompatible soft materials with tailorable functionality.


Dual Drug Release
High Internal Phase emulsions
Synergistic anti-bacterial effect
G-Quadruplex hydrogel
Cascade reaction


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