# Novel Small-Molecule Treatment and Emerging Biological Therapy for Poriasis
## 1 Introduction  
Psoriasis, marked by clear-edged, reddish plaques covered with shiny, silvery-white scales, is an autoimmune skin disease typically appearing on the elbows, knees, scalp, back, and nails [1]. Psoriasis affects about 125 million people globally, with regional prevalence variations affecting 0.14% of the population in East Asia at its low end and 1.99% in Australasia at its high end [2]. There is no gender distinction in its epidemiology in most regions. Its prevalence and incidence are lower in children than in adults [3]. The peak incidence generally appears at ages 35-44 and 50-54 [4]. In 2024, the worldwide market for psoriasis therapies reached a valuation of USD 31.61 billion. The compound annual growth rate is estimated as 8% for the decade spanning 2024 to 2034, indicating that the market will surge to USD 68.24 billion in 2034 [5]. The disease manifests in five primary forms: plaque, guttate (or eruptive), inverse, pustular, and erythrodermic. Psoriasis arises from the intricate interaction of genetic and environmental influences, particularly in individuals carrying the HLA-C*06:02 risk allele. External stimulations, such as wounds, stress, smoking, poor dietary habits, certain medications, and alcohol intake, also play a significant role [6]. The HLA-C*06:02 allele has been identified by studies as a high-risk gene that participates in psoriasis pathogenesis. This allele encodes the major histocompatibility complex class I (MHC I), enabling the presentation of autoantigens to T cells [7] and melanocytes [8] and enhancing autoimmune responses, which contribute to the pathogenesis of psoriasis [9]. External factors, such as trauma, infection, or certain medications, can trigger the secretion of self-nucleotides. These biomacromolecules combine with antimicrobial peptides produced in an inflammatory situation to form complexes. These molecular complexes subsequently engage with plasmacytoid dendritic cells (pDCs) and membrane receptor Toll-like receptors (TLRs), stimulating the secretion of interferon-\(\alpha\) (IFN-\(\alpha\)) and interferon-\(\beta\) (IFN-\(\beta\)). The released interferons activate myeloid dendritic cells (mDCs), which subsequently produce proinflammatory cytokines, including interleukin-12 and -23 and tumor necrosis factor (TNF). IL-23 interacts with receptors, promoting naive T cells' transformation into specialized T helper cells 1 and 17. Once activated, TH1 cells release TNF-\(\alpha\); TH17 and TH22 cells produce IL-17A, IL-17F, and IL-22. TNF-\(\alpha\) attracts more immune cells by exacerbating inflammatory responses, leading to their accumulation in affected skin areas. IL-17A and F activate keratinocytes to secret antimicrobial peptides, chemokines, and other inflammatory mediators, further exacerbating inflammation. IL-22 promotes keratinocyte proliferation and disrupts the skin barrier function. These signaling molecules trigger the excessive growth of keratinocytes, elevate the production of angiogenesis-promoting factors, and enhance the expression of adhesion molecules and the production of more proinflammatory molecules, creating a self-sustaining inflammatory loop [10]. The approach to managing psoriasis is tailored based on the severity of symptoms. For mild cases, local treatments are considered the most effective option [11]. Corticosteroids, analogs of vitamin D3, inhibitors of calcineurin, retinoids, and immunosuppressants, which are primarily small-molecule drugs, are used for treatment [12]. The drugs typically prescribed for psoriasis treatment include clotechasol propionate, betamethasone, calcipotriol, taxarotene, tretinoin, and methotrexate. These medications can be used either individually or in combination, administered through various topical formulations, such as creams, gels, pastes, lotions, ointments, and sprays [13]. With the development of technology, a diversity of nanocarriers have been designed to rectify the defects of traditional approaches regarding low bioavailability, systemic side effects, frequent dosing requirements, etc.