Hybrid hydrogel driven by inversely coupled thermogelation: Integrating self-assembled surfactant tubes with a block copolymer scaffold for smart delivery

Polymeric hydrogels are traditionally employed as drug reservoirs in topical delivery, but they can also function as scaffolds for drug-loaded nanocarriers, enabling hybrid systems with enhanced performance. In this work, we report a thermo-adaptive hybrid hydrogel—composed of a block copolymer scaffold and a network of surfactant-based nano- and microtubes—which exhibits a mechanism herein termed inversely coupled thermogelation (ICT). The scaffold consists of Pluronic F127, a biocompatible triblock copolymer that transitions from micellar solution to a cubic liquid crystalline gel upon heating. The tubular network arises from the self-assembly of biomimetic lysine-derived surfactants. Crucially, when the block copolymer/surfactant hybrid is heated from 20 °C to 35 °C (approx. skin temperature), the surfactant tubes disassemble into micelles or vesicles, while the block copolymer forms the cubic phase. Accordingly, a tube-dominated gel evolves into a block copolymer-dominated gel through a gel–solution–gel sequence uniquely driven by the opposing thermal responses of the two constituents. This results in a hybrid system that is not only spreadable, self-healing, and mechanically robust, but also well-suited for sustained topical delivery. Imaging, calorimetry, and rheology provide detailed insights into the structure, phase transitions, and flow behavior of the hybrid system and its individual components. As a proof-of-concept, the gel enables slow, sustained release of a fluorescent model probe (carboxyfluorescein), exhibits excellent cytocompatibility, and promotes high cell internalization. Overall, this ICT-based strategy establishes a versatile and sustainable platform with strong potential for long-term topical drug delivery. • Thermo-adaptive hybrid hydrogel composed of polymer scaffold and surfactant tubes. • Original, smart release mechanism termed inversely coupled thermogelation (ICT). • Polymer transitions from micelles to cubic phase gel, while tubes melt into vesicles or micelles. • Spreadable, self-healing, and mechanically robust hybrid gel, well-suited for topical delivery. • High cytocompatibility and high cell internalization, enabling slow, sustained probe release.