Psoriasis is an immune disease caused by rapid and incomplete differentiation of skin basal cells. Natural products such as indirubin have historically served as excellent sources for the treatments of psoriasis. However, the poor solubility and bioavailability due to its plane and rigid crystal structure, which limits its efficacy. Herein, to improve the efficacy of indirubin, a hydrogel-based microemulsion drug delivery system was developed for transdermal delivery. The mean droplet size of the optimized microemulsion was 84.37 nm, with a polydispersity index (PDI) less than 0.2 and zeta potential value of 0~−20 mV. The transdermal flux and skin retention of indirubin at 24 h were 47.34 ± 3.59 μg/cm² and 8.77 ± 1.26 μg/cm², respectively. The optimized microemulsion was dispersed in carbomer 934 hydrogel to increase the consistency. The indirubin-loaded microemulsion gel was tested on an imiquimod-induced psoriasis mouse model. Results showed that this preparation can improve psoriasis symptoms by down-regulating the expression of IL-17A, Ki67, and CD4⁺T. This experiment provides great scalability for researchers to treat psoriasis, avoid first-pass effects, and increase the concentration of targeted drugs.

Engineered hydrogels with excellent mechanical properties and multi-functionality have great potential as soft electronic skins, tissue substitutes and flexible robotic joints. However, it has been a challenge to construct multifunctional hydrogels, especially when integrating high stretchability, toughness and strength, low hysteresis, good self-healing and adhesion abilities into a hydrogel system simultaneously. Here, we successfully developed a structural hydrogel composed of a reversible covalently cross-link-based poly-N-(2-hydroxyethyl)acrylamide (PHEMAA) network and available plastically deformable casein micelles. Such a design enabled the reversible covalent cross-links and casein micelles to enhance energy dissipation and toughen the PHEMAA/casein hybrid hydrogel synergistically. More importantly, the hydrogel could respond to the imposed strains reversibly by cross-link and micelle deformation induced-network reconstitution, which led to low hysteresis of the hydrogels. The recoverable gel networks still exhibited their effects on energy dissipation at the stress-focused area, endowing the hydrogels with fatigue resistance. As a result, the hydrogels exhibited a compressive strength of 36.5 MPa, high stretchability (1460%), high toughness (∼5.98 MJ m⁻³), low hysteresis (<30%) and fatigue resistance with almost completely overlapped hysteresis curves during 10 loading cycles. In addition, the introduction of casein micelles and reversible covalent bonding endowed the elastomer hydrogels with high adhesivity, self-healing abilities and biocompatibility.