Bioinspired Antifreezing Eutectogel: A Platform for Skin Protection and Sustained Co-Drug Delivery in Extreme Cold Environments

Prolonged cold exposure can cause ice crystal formation in tissues, leading to cellular damage and frostbite, underscoring the critical need for advanced prophylactic approaches that can mitigate the limitations of existing therapies. Inspired by the natural antifreeze mechanisms of Arctic organisms, we developed an antifreezing eutectogel to safeguard skin under extreme cold conditions. Mimicking nature’s ability to inhibit ice crystallization and retain moisture, the eutectogel is formulated through synergistically interacting biocompatible Deep Eutectic Solvents (DESs) with a biocompatible metal organic framework (MOF); MIP-202 in the presence of biopolymer carboxymethyl cellulose sodium salt (CMC-Na). The structural integrity of MIP-202 and DES remained intact throughout the eutectogel formation, ensuring the retention of their properties. The eutectogels demonstrated outstanding multifunctionality, combining robust antifreeze properties, self-healing ability, strong adhesion, and excellent spreadability, while exhibiting an extraordinary drug (ibuprofen) loading capacity, exceeding 5 orders of magnitude higher than in aqueous solutions. In vitro permeation studies using Franz diffusion cells demonstrated sustained release profiles for ibuprofen and heparin, with superior permeability efficiency observed in ethylene glycol-based eutectogel (D-BE) compared to that in glycerol-based eutectogel (D-BG) (D-BE > D-BG). Beyond drug delivery, the eutectogels displayed potent antimicrobial, antifungal, anti-inflammatory, and antioxidant activities, coupled with outstanding biocompatibility with HaCaT cells and hemocompatibility, as shown by hemolysis rates below 2%. Cellular uptake assays confirmed efficient internalization of the drug-loaded gels by HaCaT cells, while in vitro migration studies revealed accelerated wound healing potential through enhanced cell migration. The antifreeze properties of the eutectogel make it highly suitable for low-temperature applications, offering effective protection against frostbite and sustained therapeutic performance under extreme conditions.