Elastomeric Protein Bioactive Eutectogels for Topical Drug Delivery

Therapeutic deep eutectic solvents (THEDES) are an emerging family of eutectic mixtures gaining increasing interest in the biomedical space. The immobilization of THEDES into polymer networks allows bioactive eutectogels to expand their application scope to topical drug delivery. Herein, this work presents the first set of elastomeric eutectogels constructed by supporting a therapeutic eutectic system with skin permeation ability in a protein scaffold dynamically crosslinked by a natural polyphenol. In this ionic eutectic, gelatin undergoes gelation through an unexpected mechanism in striking contrast with classical hydrogels, which is herein thoroughly studied. Interestingly, the polyphenol controls the conformation of the protein structure, enabling tuning up the mechanical and viscoelastic behavior of the dynamic eutectogel networks from elastic to hyperelastic. The resultant protein eutectogels exhibit strain-hardening behavior, thermoreversible gel-to-sol transition, and excellent adhesive performance. Furthermore, these versatile materials retain the bioactivity of the liquid THEDES and favor skin occlusion, assisting the delivery of both hydrophilic and hydrophobic substances in ex vivo porcine skin in a time-dependent penetration process. These ultrastretchable eutectogels show new interplays between protein scaffolds and eutectic mixtures, paving the way for innovative therapeutic soft materials. Protein elastomers are fabricated from a bioactive deep eutectic solvent with skin permeation ability. By incorporating a natural polyphenol, a transition from elastic to hyperelastic behavior is detected in these eutectogels driven by the generation of hydrogen-bonded protein nanodomains. The resulting eutectogels are not skin-irritating and exhibit a remarkable capacity to permeate both hydrophobic and hydrophilic substances through the skin.image