Development of a Deep Eutectic Solvent-Assisted Kaempferol Hydrogel: A Promising Therapeutic Approach for Psoriasis-like Skin Inflammation

Abstract

Psoriasis is an incurable inflammatory skin disease that is mediated by the immune system. Although kaempferol has been known for its anti-inflammatory, antioxidant, and anticancer properties, its therapeutic effectiveness is often limited due to its poor water solubility and low bioavailability. To address these challenges, we developed a promising kaempferol hydrogel (DK-pGEL) using Pluronic F127 and a deep eutectic solvent (DES) with varying concentrations of kaempferol. In this study, we first evaluated the rheological properties and viscosity of the DK-pGEL hydrogel. The G′ of DK-pGEL (∼14 kPa) hydrogels was significantly lower than the control group (∼30 kPa) at 37 °C. The DK-pGEL hydrogel exhibited ideal fluidity and viscosity at 37 °C, as demonstrated by its shearthinning behavior. Moreover, the DK-pGEL hydrogel showed controlled release characteristics with a drug release of 97.43 ± 5.37 μg/mL over 60 h. Furthermore, in vitro antioxidant experiments revealed that DK-pGEL exhibited significant radical scavenging ability against the DPPH-radical (96.27 ± 0.37%), ABTS-radical (98.11 ± 0.79%), hydroxyl-radical (66.36 ± 1.01%), and superoxide-radical (90.52 ± 0.79%) at a concentration of 250 μg/mL kaempferol. Additionally, DK-pGEL exhibited notable cellular antioxidant effects by inhibiting reactive oxygen species generation. Cell viability assays (CCK8) and live/dead cell assays were conducted to assess the cytotoxicity of DK-pGEL. The results showed that DK-pGEL could effectively inhibit HaCaT cell proliferation without causing significant cytotoxicity. To evaluate the therapeutic potential of DK-pGEL, an imiquimod (IMQ)-induced mouse model of psoriasis-like lesions was employed. Remarkably, the DK-pGEL hydrogel could significantly reduce the psoriasis area and severity index score, improve the histopathology induced by IMQ, and downregulate the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-17A) in the skin tissue. These findings demonstrate that the DES-assisted kaempferol hydrogel holds promise as a topical drug delivery system for psoriasis treatment.

Recent Advancements and Trends of Topical Drug Delivery Systems in Psoriasis: A Review and Bibliometric Analysis

“… [ 119 ] Pluronic F127, choline chloride - - Kaempferol BALB/c mice It reduces both the Psoriasis Area and Severity Index (PASI) score and downregulates the expression of specific pro-inflammatory cytokines. [ 120 ] Polyvinylpyrrolidone (PVA/PVP) K-90 polymeric blend 252.31 ± 35.50 nm Electrospinning technique, solvent casting method Tazarotene, calcipotriol Wistar rats It exhibited a prolonged release pattern over an extended period and demonstrated potential antipsoriatic activity by promoting the regeneration of the epithelial layer. [ 121 ] Polysorbate 80, isopropyl myristate, water, alkylated carbomer - Aqueous titration Methotrexate Swiss mice It is indicated for localized psoriasis treatment.…”

“… 116 Su, H. et al formulated a kaempferol hydrogel with controlled-release properties that scavenged over 90% of free radicals at specific concentrations, also inhibiting HaCaT cell proliferation without significant cytotoxicity; in mouse models, it markedly reduced psoriasis symptoms and pro-inflammatory cytokines TNF-α, IL-6, and IL-17A. 120 Sunita Thakur et al created a tazarotene-CT-loaded nanofiber and carbopol-based hydrogel film that biodegraded within two weeks, achieving nearly 96% drug release in 72 hours with anti-psoriatic solid effects in a mouse model. 121 Rana, K. et al used a cholic acid-dipeptide conjugate for self-assembly in a betamethasone-loaded hydrogel, enhancing the steroid’s solubility and release properties.…”