Ludwika Piwowarczyk

Nanocarrier-based delivery of 20-hydroxyecdysone modulates IL-17/IL-23 signaling in psoriasis model

Piwowarczyk Ludwika¹, Majchrzak-Celińska Aleksandra², Kleszcz Robert², Musielak Ewelina², Gajewska Julia ²,Szkudlarek Jagoda¹, Czerniel Joanna¹, and Krajka-Kuźniak Violetta²

¹ Poznan University of Medical Sciences, Department of Pharmaceutical Chemistry, Rokietnicka 3, Poznań, Poland
² Poznan University of Medical Sciences, Department of Pharmaceutical Biochemistry, Rokietnicka 3, Poznań, Poland

Abstract
Psoriasis is a chronic inflammatory skin disease characterized by dysregulated immune responses and epidermal hyperproliferation, in which cytokine networks involving IL-17 and IL-23 play a central pathogenic role [1]. Keratinocytes actively contribute to this process by producing pro-inflammatory mediators and sustaining local immune activation. Despite advances in systemic therapies, effective topical strategies targeting these pathways remain limited due to the impaired barrier function of psoriatic skin [2]. 20-Hydroxyecdysone (20-HE), a natural phytoecdysteroid, exhibits anti-inflammatory, antioxidant, and cytoprotective properties, but has limited skin penetration and bioavailability. Therefore, lipid-based nanocarrier delivery systems have been developed to enhance dermal delivery and improve the biological activity of active compounds [3]. In this study, lipid-based nanocarrier formulations containing 20-HE were developed and characterized, and their biological activity was evaluated in human epidermal keratinocytes (HEKs) and psoriasis-derived keratinocytes (PHEKs). Cells were treated with the respective nanoformulations for 48 hours. Cytokine levels, including IL-17A and IL-23, were quantified using a Western blot assay. All tested nanoformulations of 20-HE modulated inflammatory responses in keratinocytes, with differential effects depending on the carrier type. In conclusion, nanoformulations containing 20-HE exhibit distinct anti-inflammatory profiles in psoriatic keratinocytes. Modulation of IL-17/IL-23-associated signaling highlights the potential of these nanocarrier systems to become promising candidates for topical psoriasis therapy.

References
[1] Li, L.; Liu, J.; Lu, J.; Wu, J.; Zhang, X.; Ma, T.; Wu, X.; Zhu, Q.; Chen, Z.; Tai, Z. Interventions in cytokine signaling: novel horizons for psoriasis treatment. Front Immunol. 2025, 16, 1573905.
[2] Liu, Y.; Chang, R.; Deng, H.; Liang, F.; Xu, X.; Luo, Y. Advances in the Drug Delivery Systems for Psoriasis Topical Therapy. Int J Nanomedicine 2025, 20, 12307-12329.
[3] Kang, Y.; Zhang, S.; Wang, G.; Yan, Z.; Wu, G.; Tang, L.; Wang, W. Nanocarrier-Based Transdermal Drug Delivery Systems for Dermatological Therapy. Pharmaceutics 2024, 16, 1384.

Funding: “Research aimed at developing a new, innovative pharmaceutical form for the topical treatment of psoriasis vulgaris” is being implemented as part of the National Recovery and Resilience Plan, as part of Investment D3.1.1 Comprehensive development of research in medical sciences and health sciences, reference number: 2024/ABM/03/KPO/KPOD.07.07-IW.07-0043/24-00.