Tehran University of Medical Sciences Traditional and Integrative Medicine 2476-5104 11 2 2026 06 30 2446 2446 Siddhi Fogueri Department of Pharmacognosy, KLE College of Pharmacy, JNMC Campus, Nehru Nagar, Belagavi-590010, Karnataka Mrityunjaya Patil Department of Pharmacognosy, KLE College of Pharmacy, JNMC Campus, Nehru Nagar, Belagavi-590010, Karnataka 2025 10 03 2026 02 15 This study focuses on developing a novel topical silver nanoparticle (AgNPs) based gel for psoriasis, a chronic inflammatory skin disease affecting over 60 million people worldwide. Conventional therapies are limited by side effects and poor efficacy, highlighting the need for safer and more effective alternatives. Kaempferol (KMP), a natural flavonoid with anti-psoriatic activity, has poor solubility and low bioavailability. To overcome these limitations, kaempferol-silver nanoparticles (KSNPs) were synthesized and incorporated into a quercetin (QRT) gel. The efficacy of the KSNP-loaded QRT gel was assessed through in vitro studies in human keratinocytes, skin irritation testing, and in vivo evaluation in an imiquimod (IMQ)-induced psoriasis model. The formulation aims to enhance skin penetration, stability, and therapeutic outcomes, providing a promising strategy for improved psoriasis management. The formulation exhibited 89.54 ± 1.27% entrapment efficiency with 85.15% cumulative drug release over 24 hours. In vitro assays (HRBC membrane stabilization and protein denaturation inhibition) confirmed strong anti-inflammatory activity, while skin irritancy studies indicated reduced toxicity through KMP-mediated bio-reduction of silver nanoparticles. In the IMQ-induced psoriasis model, topical application of the gel marked a visible reduction in PASI scores, further supported by histopathological evidence. Overall, the KSNP-loaded QRT gel, combining the complementary effects of KMP and QRT, demonstrated controlled drug release and promising therapeutic efficacy for psoriasis and related inflammatory skin disorders. The KSNP-loaded QRT gel shows a promising, safe, and effective topical therapy for psoriasis, leveraging the anti-inflammatory effects of KMP and QRT with enhanced bioavailability through nanoparticle formulation. https://jtim.tums.ac.ir/index.php/jtim/article/view/2446