Eugenol loaded lipid nanoparticles derived hydrogels ameliorate psoriasis-like skin lesions by lowering oxidative stress and modulating inflammation

Abstract

AbstractPsoriasis is a chronic T-cell-mediated autoimmune skin disorder characterized by excessive epidermal thickening, keratinocyte over-proliferation, disruption of epidermal cell differentiation, and increased blood vessel growth in the dermal layer. Despite the common use of corticosteroids in psoriasis treatment, their limited efficacy and numerous side effects pose significant challenges. This research introduces a promising alternative approach by presenting hydrogels loaded with Eugenol (EU) in combination with Carbopol 974P (EUNPGel) for potential psoriasis management. EUN-loaded lipid nanoparticles (EUNPs) exhibit superior drug loading, enhanced release kinetics, long-term stability, and the ability to scavenge reactive oxygen species (ROS). Furthermore, EUNPs have been shown to inhibit keratinocyte proliferation, induce apoptosis, and augment the uptake of IL-6-mediated inflammation in human keratinocyte cells. Application of EUNPs-loaded gels (EUNPGel) to imiquimod-induced psoriatic lesions has demonstrated effective dermal penetration, suppressing keratinocyte hyperplasia and restoring epidermal growth. This led to a remarkable reduction in the Psoriasis Area and Severity Index (PASI) score from 3. 75 to 0. 5 within five days. These findings highlight the potential of EUNPGel as an innovative nanomedicine for treating inflammation. This novel approach enhances ROS scavenging capacity, improves cellular uptake, facilitates skin penetration and retention, reduces the activity of hyperactive immune cells, and suggests potential applications for treating other immune-related disorders such as acne and atopic dermatitis.HighlightsHydrogel loaded with eugenol is an innovative alternative for psoriasis management.Superior drug loading, release kinetics, stability, and ROS scavenging capacity.Curb (human keratinocyte) HaCaT cells proliferation, induce apoptosis, lower IL-6 mediated inflammation.Effective dermal penetration and retention both in vivo and ex vivo.