Emerging Therapeutic Agents and Nanotechnology-Driven Innovations in Psoriasis Management

Abstract

Psoriasis has been a rising concern for over a decade, imposing significant challenges to individuals and society. Traditional topical therapy is non-targeted and acts systemically, with associated side effects. This increases the global burden both socially and economically. This review covers the evolution of drug molecules and nanotechnology-based approaches for the topical treatment of psoriasis, a chronic inflammatory skin disorder with no known etiology. Nanotechnology-based approaches offer promising solutions by reducing side effects, providing targeted delivery, protecting drug molecules from degradation, enhancing skin retention, and providing controlled release. Researchers have investigated the incorporation of various conventional and non-conventional therapeutic agents into nanocarriers for psoriasis treatment. The current understanding of the disease and its treatment using various therapeutic agents combined with novel formulation strategies will reduce the duration of treatment and improve the quality of life in psoriatic disease conditions.

Graphical abstract

Keywords

psoriasis / topical drugs / delivery systems / inflammatory cytokines / nanotechnology

1. Introduction

The management of psoriasis, a chronic inflammatory skin disorder, requires innovative therapeutic approaches to overcome the limitations of traditional treatments. Natural agents are widely valued for their diverse biological effects and low side-effect profiles. A comprehensive approach integrating a healthy lifestyle, natural medicines, emerging drugs, and nanotechnology offers promising advancements. The integrative approach not only enhances treatment efficacy but also contributes to reducing the overall burden of psoriasis, improving patient outcomes and quality of life [1, 2]. Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia and hyperkeratosis. In psoriasis, the skin undergoes various changes, manifesting as itchiness, redness, inflammation, scaliness, and emergence of skin lesions (Fig. 1) [3]. The prevalence of psoriasis varies, ranging from 0.27% to 11.4%, depending on genetic factors, sex, age, environment, ethnicity, and geography. It affects approximately 64.6 million people worldwide [4]. Psoriasis can affect the skin, nails, scalps, and joints. It is also associated with various comorbidities such as cardiovascular diseases, cancer, diabetes, anxiety, and depression. Common inflammatory pathways, genetic susceptibility, cellular mediators, and risk factors have been hypothesized to play contributory roles. Psoriasis affects quality of life at the physical, psychological, and social levels, resulting in poor mental health, reduced productivity, and even social exclusion [5].

Psoriasis is an autoimmune condition that is triggered by the activation of T lymphocytes. Activated T lymphocytes increase the infiltration of inflammatory cytokines in the dermis and marginally in the systemic circulation, thereby increasing the proliferation of keratinocytes and epidermal cell turnover [6]. One-third of patients with psoriasis have a genetic background. Various factors such as infection, stress, metabolic syndrome, obesity, and diabetes can also trigger it. These triggers can damage the skin, leading to a repair response in which skin keratinocytes undergo excessive proliferation without adequate differentiation. This abnormal process results in an impaired skin barrier and the formation of scaly plaques [7].

Management of psoriasis involves a multifaceted approach including adopting a healthy lifestyle and integrating therapeutic interventions. Key lifestyle modifications include effective stress management, regular physical activity, smoking cessation, avoiding alcohol consumption, maintaining an active skincare routine, dietary modification to reduce systemic inflammation, and utilizing therapeutic agents—essential components of a comprehensive management strategy [8, 9].

Many review articles have described various topical nanotechnology-based formulations and therapeutic agents available for the management of psoriasis [6, 10, 11]. However, study on emerging topical therapeutic agents are still required. Unlike previous reviews, it critically evaluates the integration of emerging and conventional therapies with nanocarriers. The present study attempts to provide insights into the existing state of research on topical therapeutics effective for psoriasis and proposes directions for future research. Using the query “TITLE-ABS-KEY (topical AND “drug delivery” AND psoriasis) AND (LIMIT-TO (DOCTYPE, “ar”)) AND (LIMIT-TO (LANGUAGE, “English”))”, Scopus and PubMed were retrieved at the mid of 2024. A total of 512 articles were retrieved by mid-2024, of which 207 duplicates were removed, leaving 305 articles for review. A total of 132 studies were scanned from 305 articles to confirm that only the relevant studies of interest were selected. After reviewing the title, abstract, and keywords, 156 articles were removed, and 37 were removed after reading the full text. A total of 112 articles were selected for this study.

2. Pathophysiology of Psoriasis

Psoriasis is a multifactorial disease triggered by stress-induced keratinocyte damage due to various factors. Its pathophysiology involves multiple components, including immune cells, genetic predispositions, antimicrobial peptides, and non-coding RNAs (Fig. 2). Psoriasis is an immune-driven condition characterized by T lymphocyte activation. Dendritic cells, which function as antigen-presenting cells (APCs), initiate an immune response by generating interleukin -12 (IL-12) and interleukin -23 (IL-23), prompting the activation of T helper 1 (Th1) and T helper 17 (Th17) cells. Th1 cells generate tumor necrosis factor-\alpha (TNF-\alpha) and interferon-\gamma (IFN-\gamma), whereas Th17 cells produce IL-22, IL-17A, and IL-17F. These inflammatory cytokines play pivotal roles in stimulating keratinocyte proliferation (Fig. 3). TNF-\alpha specifically contributes to an increase in inflammatory cell infiltration.

Additionally, Langerhans cells serve as mediators in activating distinct types of T cells such as natural killer (NK) cells and NK-T cells. Th1 and Th2 utilize the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway to perform their functions. In contrast, Th17 cells operate through the activator 1 (ACT1) adapter protein and nuclear factor kappa B (NF-\kappaB) signaling mechanism. Macrophages produce TNF-\alpha and vascular endothelial growth factor (VEGF), which further increases inflammation and blood vessel growth. T-cell activation increases keratinocyte proliferation, and keratinocytes produce various growth factors and cytokines, which increase proliferation and inflammation [12]. Chemokine receptors, such as the C–X–C motif chemokine receptor (CXCR) superfamily, play an important role in initiating the innate immune response by activating and migrating immune cells. CXCRs are important for tissue healing and pathogen elimination, but their overactivation results in a T-cell-mediated immune response, increased inflammatory response, and psoriasis [13]. Although not as pivotal as T cells, B cells also play a role in the initiation and progression of psoriasis; when triggered by autoantigens, they induce molecular mimicry, influencing B-cell behavior in gastric centers (GCs), producing autoantibodies and proinflammatory cytokines, forming ectopic germinal centers, and dysregulating proliferation of keratinocytes [14].

Psoriasis is associated with significant changes in gene expression. Psoriasis occurs more frequently in monozygotic twins than in dizygotic twins. It is activated by environmental factors in individuals with genetic predisposition. Approximately 60 psoriasis-susceptible regions have been identified. According to linkage analysis, nine loci known as psoriasis-susceptible (PSOR1-9) are responsible for disease susceptibility. PSORS-1 was the most validated, whereas a weaker linkage was observed in PSORS-2 and PSORS-4. Linkage in the remaining regions was not replicated in independent research. PSORS-1 is the major histocompatibility complex (MHC) locus on chromosome 6p21. The 150 kb region of MHC-1 contains nine genes, of which three, CCHCR1, HLA-C, and CDSN, are significantly related to psoriasis. HLA-C codes for MHC class I receptors that participate in the immune response by acting as an antigen for CD8+ lymphocytes. In the PSORS-2 locus, the mutation in CARD14 is responsible for the phenotype of plaque and pustular psoriasis. PSORS-4 is located on the 1q21 chromosome; it stretches the epidermal differentiation cluster (EDC). Absence of the EDC gene is associated with psoriasis [15].

Antimicrobial peptides (AMPs) are 12–50 amino acid long, amphiphilic molecules. Keratinocytes, T cells, dendritic cells, and neutrophils secrete antimicrobial peptides such as S100, \beta-defensin, and cathelicidin. They activate the innate immune response to induce inflammation in psoriasis patients. Plasmacytoid dendritic cells (DCs) and neutrophils are critical components of the innate immune system. Antimicrobial peptides enhance the affinity between damage-associated self-DNA and self-RNA and their corresponding receptors. This heightened interaction subsequently amplifies keratinocyte interferon secretion and activates plasmacytoid dendritic cells. Consequently, this process actively stimulates and intensifies the inflammatory responses. Neutrophils release neutrophil extracellular traps (a complex of IL-33 and self-DNA), thereby inducing Th17 activation. Activated myeloid dendritic cells release inflammatory cytokines IL-12, IL-17, and IL-23. Antimicrobial peptides also increase the production of Th1 and Th17 cells. Therefore, AMPs play a vital role in psoriatic inflammation by activating the innate immune response [16, 17].

Non-coding RNAs such as microRNAs (mRNAs) and long non-coding RNAs (lncRNAs) also play a role in the pathogenesis of psoriasis. More than 250 mRNA were atypically expressed in psoriatic lesions. Some mRNAs were upregulated, whereas others were downregulated. For example, mRNA miR-31 is upregulated; therefore, deletion of miR-31 alleviates inflammation and hyperplasia of keratinocytes. Conversely, miR-14a/b is highly expressed in psoriatic lesions and negatively regulates keratinocyte proliferation—so it has a protective effect. Genetic deficiency of miR-14a exacerbates psoriatic inflammation. lncRNAs control gene expression at both the transcriptional and post-transcriptional levels. In psoriasis, the non-protein-coding RNA induced by stress (PRINS), a type of lncRNA, is significantly overexpressed in the epidermis of affected patients. PRINS is activated by stress and its silencing decreases keratinocyte viability under stress conditions. However, the lncRNA maternally expressed gene 3 (MEG3) is downregulated in psoriatic skin. MEG3 suppresses keratinocyte proliferation and enhances apoptosis by targeting miR-21 and increasing Caspase 8 expression [18].

3. Treatment of Psoriasis

The available treatments for psoriasis aim to alleviate symptoms and improve the patient’s quality of life, as psoriasis is a chronic disease with no cure and requires long-term treatment. This creates economic challenges for the healthcare and pharmaceutical industries [19]. Treatment of psoriasis consists of combinations of therapeutic agents to address complications of psoriasis depending on the severity of the disease, patient-specific factors, and the presence of co-morbidities. The therapeutic agents alleviate symptoms, improve skin health, and enhance the quality of life for patients. Broadly, therapeutic approaches can be categorized into topical treatments, systemic therapies, and advanced biologics. While topical treatments remain the cornerstone for managing mild to moderate psoriasis, systemic therapies and biologics are pivotal for severe cases. Topical agents are the first-line treatment for mild to moderate cases. Topical agents include corticosteroids, vitamin D derivatives, retinoids, anthralin, and salicylic acid (SA). Potent and super potent corticosteroids are as effective as vitamin D derivatives and can be combined with keratolytic agents, such as salicylic acid, to treat thick scaling. Vitamin D derivatives can be used alone or with corticosteroids but should not be used with keratolytics or phototherapy [3]. Systemic agents are used to treat moderate-to-severe psoriasis. Systemic agents include the following: retinoids, such as acitretin; immunosuppressants, such as methotrexate and tacrolimus; and immunomodulators, such as cyclosporin. These agents can cause serious side effects, such as nephrotoxicity, hepatotoxicity, and increased risk of infection. Therefore, these agents are unsuitable for long-term treatment. Retinoids are teratogenic and should not be used for women of childbearing age [20]. Phototherapy is used in moderate-to-severe psoriasis; it includes narrow- and broad-band Ultraviolet B (UV-B) and Ultraviolet A (UV-A) therapy with or without psoralen. Challenges associated with phototherapy include the limited number of centers available, frequent visits, cost, and increased risk of skin cancer [21]. Biologicals are a relatively new treatment approved by the US FDA (United States Food and Drug Administration) and are used to treat moderate to severe psoriasis but are costly and lack long-term safety data. Biological agents included TNF-\alpha inhibitors (infliximab, etanercept, and adalimumab), IL-12/23 inhibitors (ustekinumab), IL-17 inhibitors (ixekizumab, secukinumab), and IL-23 inhibitors (guselkumab, risankizumab, and tildrakizumab). Biologicals suppress the immune response, increasing the risk of infection and cancer [21, 22]. Although there are many therapeutic agents available for the treatment of psoriasis, they are associated with side effects and limitations in their long-term efficacy. There remains an urgent need for the development of novel therapeutic agents that specifically target the molecular pathways underlying psoriasis. These agents should offer greater specificity for the disease, minimize adverse effects, and provide sustained effectiveness over extended treatment periods, thereby improving overall patient outcomes. Emerging drugs, such as aryl hydrocarbon receptor (AhR) agonists, offer a novel approach to treating psoriasis by regulating keratinocyte function. These drugs help to restore normal skin barrier function, which is often compromised in psoriatic skin [23]. RNA-based approaches hold significant promise for the future of psoriasis treatment. These technologies offer the potential for highly specific, targeted therapies that directly address the underlying molecular mechanisms driving the disease [24]. Numerous natural compounds are under investigation for their potential to complement existing treatments. Many of these compounds, including antioxidants from plant extracts, have demonstrated the ability to reduce oxidative stress, a key factor in the inflammation and skin damage seen in psoriasis. By mitigating oxidative damage, these natural agents can act as adjuvant therapies, potentially enhancing the effectiveness of conventional treatments like corticosteroids or biologicals [2]. Their ability to synergize with standard therapies offers a multi-faceted approach to treatment, potentially improving therapeutic outcomes, reducing side effects, and providing a more holistic approach to disease management.

4. Topical Therapeutics in Psoriasis and Their Mechanism of Action

Topical treatment is effective in most patients with psoriasis, and only 20% require systemic therapy [25]. Glucocorticoids, the primary drugs used for treating psoriasis, were first introduced in the 1950s, followed by the development of immunosuppressants and retinoids. Treatment has advanced significantly with the approval of vitamin D analogs in the 1990s, followed by the introduction of TNF-\alpha inhibitors in the 2000s, marking a major leap in targeted biological therapies. RNA-based treatments are still under investigation and no drugs have been approved to date. Fig. 4 illustrates the historical evolution of psoriasis treatments. This review focuses on drugs, ranging from those in the initial investigational stages to those already approved. Drugs that are currently in the pipeline, undergoing clinical trials, or recently approved by the US FDA are discussed in detail elsewhere [26].

4.1 Glucocorticoids

Glucocorticoids are the first-line treatment, either alone or in combination. It has multiple functions, including antimitotic, anti-inflammatory, immunomodulatory, and vasoconstrictive effects. Therefore, it helps to reduce redness, swelling, scaling, and itching in psoriatic lesions. Glucocorticoids are chemically derived from androgens and pregnanes. Glucocorticoids consist of four lipophilic rings, which enable them to bind to glucocorticoid receptors [27]. Topical glucocorticoids were introduced in the 1950s and are still preferred for psoriasis management. Four classes of glucocorticoids are used to treat psoriasis: low potency (LPG), mid potency (MPG), high potency (HPG), and super high potency (SHPG). Low- and mid-potency glucocorticoids are used in folds, whereas high- and super-high-glucocorticoids are used on the exterior surfaces. Glucocorticoids act via two pathways, genomic and non-genomic. In the genomic pathway, cortisol binds to the glucocorticoid receptor, resulting in receptor dimerization and binding with the glucocorticoid responsive element (GRE), causing transcription of anti-inflammatory genes such as tyrosine aminotransferase (TAT), IL-10, antagonizing IL-1, and promoting dual-specificity protein phosphatase 1 (DUSP-1). Glucocorticoids also negatively regulate the expression of proinflammatory genes, such as cytokines, adhesion molecules, growth factors, nitric oxide, and autocoids. The non-genomic pathway does not involve de novo protein synthesis, so it rapidly affects binding to the glucocorticoid receptor, and a second messenger comes into action. It alters the activation and response of target cells such as T cells, platelets, and monocytes [27, 28].

4.2 Vitamin D3 Analogs (VDA)

The active form of VDA is calcitriol or 1,25(OH)₂D3, whereas other synthetic analogs include calcipotriol, calcitriol, maxacalcitol, and tacalcitol. The first topical treatment for VDA was calcipotriol, which was introduced in Europe in 1987 and approved by the US FDA in 1993. It reverses epidermal dysregulation and hyperproliferation and induces apoptosis. In psoriasis, reduced vitamin D receptor expression is correlated with lower tight junction protein levels, which disrupts the skin barrier. Tight junctions are essential for keratinocyte adhesion and permeability and regulate cell differentiation through interactions with nuclear and cytoplasmic proteins. Vitamin D3 promotes keratinocyte terminal differentiation and inhibits proliferation, although the exact mechanism remains unclear. It also has immunomodulatory effects. It acts on cells involved in immunologic reactions, such as macrophages, lymphocytes, and Langerhans cells [29, 30, 31, 32].

4.3 Immunosuppressors

Methotrexate is generally used as a systemic agent, but numerous topical formulations have been reported in the literature. It was introduced as a chemotherapeutic agent in the 1950s for treating cancer and autoimmune diseases, with its use in psoriasis beginning in the 1960s. Methotrexate (MTX) is a folic acid analog and antagonist. It binds to folic acid reductase with a much higher affinity than folic acid. It inhibits the synthesis of tetrahydrofolate and pyrimidine, which are required to synthesize DNA base pairs, leading to reduced DNA replication and inhibition of RNA and protein synthesis. It reduces epidermal cell proliferation and lymphocyte number [20].

Cyclosporine, a calcineurin inhibitor, was initially used as an immunosuppressant in organ transplants to prevent rejection, introduced for psoriasis treatment in the 1980s, and received FDA approval in 1997. The mechanism of action of cyclosporine is immunosuppression by binding with cyclophilin and inhibition of calcineurin, which is required for the transduction of calcium-dependent signals from T lymphocytes to cytokine promoters. It inhibits the proliferation of CD4+ helper T cells and keratinocytes. It regulates the immune system by explicitly inhibiting T-cell overproduction and impairing the function of antigen-presenting Langerhans cells. Whether taken orally or topically, cyclosporin has an affinity for skin cells. Cyclosporine reduced cell infiltration and epidermal thickness. It can be administered via a systemic or topical route; however, systemic treatment causes various side effects, which can be reduced with the use of topical formulations [20, 33, 34]. Other topical calcineurin inhibitors used for the treatment of psoriasis include tacrolimus and pimecrolimus. They exert an antipsoriatic effect by inhibiting the proliferation of T lymphocytes and dysregulation of mast cells. They do not affect fibroblasts and endothelial cells or cause skin atrophy [35].

4.4 Retinoids

Retinoids can be administered via both systemic and topical routes. Etretinate is a synthetic analog of retinoic acid approved by the FDA for oral use in the treatment of severe psoriasis in 1986. It is a metabolite of etretinate, has a shorter half-life, and is preferred as a systemic agent for managing psoriasis [36]. Tretinoin and isotretinoin are topical and systemic agents, respectively, whereas adapalene and tazarotene are topical agents. Retinoids are teratogenic when administered systemically. Retinoids have anti-hyperproliferative potential. They modulate T lymphocyte responses, inhibit chemotactic responses, activate polymorphonuclear leukocytes, and increase Langerhans cells. They also stimulate natural killer lymphocytes and induce the migration of inhibitory factor-related proteins (MRP-8) by inhibiting IFN-\gamma via retinoid receptor activation [37].

4.5 Sphingosine-1-Phosphate Receptor 1 (S1P1) Modulator

Fingolimod was the first SIP1 modulator approved by the US FDA in 2010 for oral treatment of multiple sclerosis. Owing to its success in modulating the immune response, its potential in treating autoimmune diseases, including psoriasis, has been explored [38]. AKP-11 is a highly selective sphingosine-1-phosphate receptor modulator. SIP is a lipid that binds to G protein-coupled S1P receptors and modulates cell proliferation, cell differentiation, and proinflammatory cytokine production, thus helping maintain skin barrier function. The topical formulation of AKP-11 has been used in clinical trials for psoriasis treatment [39, 40]. Similarly, HWG-35D, a sphingosine kinase 2 inhibitor, is beneficial for psoriasis. Sphingosine kinase increases the phosphorylation of sphingosine phosphate and its inhibition blocks Th17 differentiation into CD4+ T lymphocytes. The topical application of HWG-35D (a novel sphingosine kinase 2 inhibitor) normalized the systemic and local immune responses induced by imiquimod (IMQ) treatment [40].

4.6 Aryl Hydrocarbon Receptor Agonist

Tapinarof is the first aryl hydrocarbon inhibitor that received US FDA approval on May 23, 2022, to treat mild, moderate, and severe psoriasis. Tapinarof is a secondary metabolite obtained from the Gram-negative bacterium, Photorhabdus luminescens. The binding of tapinarof to the aryl hydrocarbon receptor leads to the translocation of the receptor from the cytoplasm to the nucleus after dimerization with the aryl hydrocarbon nuclear translocator, activating different genes. Aryl hydrocarbon signaling regulates Th17 and Th22 differentiation and IL-17 and IL22 expression. Tapinarof regulates keratinocyte function by inducing the expression of skin barrier genes. Therefore, it helps normalize the skin barrier disrupted by psoriasis. It reduces epidermal oxidative stress by directly scavenging reactive oxygen species and increasing the expression of antioxidant enzyme genes [23, 41].

4.7 Antimicrobial Peptides

Omiganan is a 12-amino-acid, antimicrobial cationic peptide active against many Gram-negative and Gram-positive microbes and fungi. It inhibits the activation of toll-like receptors (TLRs) on dendritic cells and other immune cells. This inhibition prevents the downstream inflammatory cascade that contributes to psoriasis. It also possesses anti-inflammatory properties. The liposomal gel formulation of omiganan substantially reduced psoriatic lesions by reducing the levels of proinflammatory cytokines [42]. Thiostrepton is a naturally occurring antimicrobial peptide that inhibits the activation of toll-like receptors 7-9 (TLR7-9) in dendritic cells. In psoriasis, these receptors are activated and contribute to the inflammatory response. Thiostrepton mitigates this activation through two primary mechanisms: the inhibition of proteasome function and endosome acidification. In mouse models, thiostrepton ameliorates psoriasis-like inflammation induced by imiquimod and LL37 [43].

4.8 Phosphodiesterase 4 (PDE-4) Inhibitors

PDE is expressed in keratinocytes and immune cells. It mediates the inflammatory response by hydrolyzing cyclic adenosine monophosphate (cAMP). Inhibition of PDE-4 increases intracellular cAMP concentrations, which activates various downstream pathways. This process inhibits the inflammatory response by suppressing the production of inflammatory cytokines and activating anti-inflammatory mediators [44]. Apremilast was the first PDE-4 inhibitor to receive US FDA approval in March 2014 for the treatment of plaque psoriasis and psoriatic arthritis. Apremilast acts as an anti-inflammatory drug by inhibiting various proinflammatory cytokines involved in the pathogenesis of psoriasis, such as TNF-\alpha, IL-6, and IL-10 [45]. Roflumilast is another highly potent PDE-4 inhibitor approved by the US and FDA in 2022 for the treatment of chronic plaque psoriasis. Blocking PDE-4 activity increases cAMP concentration, which reduces inflammatory cytokines in psoriatic skin [46, 47]. PF-07038124 is a potent PDE-4 inhibitor currently undergoing clinical trials for psoriasis treatment. It works by inhibiting cytokines IL-4 and IL-13. According to previous reports, it exhibits minimal to no adverse effects or application site reactions [26, 48].

4.9 Herbal Drugs

Many herbal drugs have been explored for their antipsoriatic activity for a long time. Curcumin has shown antipsoriatic activity, as reported in many clinical and preclinical research. Curcumin has an inhibitory effect on IL-22-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation. It also inhibits vesicular endothelial growth factor (VEGNF-\kappaBF), thus reducing vascular proliferation. It decreases the secretion of inflammatory cells and blocks the NF-\kappaB, mitogen-activated protein kinase (MAPK), and Janus kinase–signal transducer and activator of transcription (JAK-STAT) signaling pathways [49]. Other herbal drugs, such as lavender oil, rosmarinic acid, and Rosa species (R. canina, R. damascena, and R. Cairo) have anti-inflammatory and antioxidant properties [50, 51]. Berberine, an alkaloid obtained from Mahonia aquifolium has antipsoriatic activity due to its ability to suppress keratinocyte growth, inhibit DNA and protein synthesis by inhibiting enzyme reverse transcriptase, and inhibit cell proliferation in psoriasis. It also exhibits anti-inflammatory properties by inhibiting cyclooxygenase, lipoxygenase, and cytokines [52]. Silibinin, an active Silybum marianum constituent, exerts an antipsoriatic effect by inhibiting phosphorylation signals and cell proliferation [53]. Commiphora mukul and quercetin-loaded lipospheres for antipsoriatic activity have also been reported. Commiphora mukul has anti-inflammatory properties and inhibits TNF-\alpha and IFs. Quercetin has antioxidant, anti-inflammatory, and antiproliferative properties [54]. Celastrol is a pentacyclic triterpene extracted from Tripterygium wilfordii Hook f. and has anti-inflammatory, antioxidant, and anti-tumor properties. It inhibits Th17 cell differentiation, pSTAT3 activation, and downregulates the NF-\kappaB pathway [55]. Erianin, a phytochemical isolated from Dendrobium chrysotoxum Lindl inhibits keratinocyte proliferation and angiogenesis [56]. Various active ingredients of Psoralea corylifolia have been reported to be beneficial for the treatment of psoriasis [57, 58, 59]. Ursolic acid, a pentacyclic triterpenoid, can be extracted from many plants, including bearberry, thyme, lemon balm, lavender, and sage. Ursolic acid inhibits the COX-2 and NF-\kappaB signaling pathways, downregulates proinflammatory cytokines such as IL-17, and provides anti-inflammatory effects in psoriasis. It also exhibits antioxidant activity [60, 61]. Retinyl palmitate oil is a stable and natural source of retinoids, whereas dead seawater (DSW) has a high salt composition—both of which are beneficial in many skin diseases, including psoriasis [62].

4.10 Nutraceuticals

Nutraceuticals have both nutritional and medicinal properties [63]. Oleuropein, a nutraceutical product obtained from olive leaves, has anti-inflammatory and antioxidant properties, and its microemulsion formulation was found to be better than the marketed formulation Dermovate in patients with psoriasis, as reported by the authors [64]. (-)-epigallocatechin-3-gallate (EGCG), a catechin found in green tea, induces the expression of keratinocyte differentiation markers and has immunoregulatory and antiangiogenic properties [65].

4.11 Biologicals

4.11.1 TNF-\alpha Inhibitors

TNF-\alpha is a vital cytokine that increases the proliferation of cytokines. Capsaicin inhibits TNF-\alpha by inhibiting NF-\kappaB, substance P, and causes inhibition of cutaneous and axon-reflex vasodilation [66]. Etanercept, a fusion protein, acts as a TNF-\alpha and TNF-\beta inhibitor, but has a significant molecular weight. It is generally administered subcutaneously, but an ablative fractional laser (Er: YAG laser+etanercept) can deliver etanercept to the epidermis and dermis layer of the skin with low transdermal permeation [67, 68]. Etanercept received US FDA approval in 2004 for moderate-to-severe plaque psoriasis or psoriatic arthritis [69].

4.11.2 Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) Inhibitors

JAK inhibitors target specific proinflammatory cascades in psoriasis. Cytokines, such as IL-6, IL-12, IL-22, and IL-23, play a role in the development of psoriasis. They bind to type I and II receptors, which depend on JAKs for signal transduction. Upon the binding of cytokines to their receptor, receptors undergo conformational changes and activate and recruit two JAK proteins. Upon activation, JAK alters the receptor, allows binding of STAT proteins, and results in phosphorylation, dimerization, and translocation to the nucleus to change gene expression. There were four JAK and seven STAT proteins. Inhibition of each subtype of JAK can disrupt various downstream signaling pathways, making it an effective treatment for reducing inflammation in psoriasis [70]. Deucravacitinib is an oral drug approved by the US Food and FDA for the treatment of moderate-to-severe psoriasis. It is a tyrosine kinase 2 (TYK2) inhibitor, a member of the JAK family of inhibitors [71]. Topical JAK inhibitors include tofacitinib, ruxolitinib, and baraticinib. Baraticinib inhibits JAK1 and JAK2 activities by disrupting the production of downstream signaling molecules and proinflammatory mediators. Tofacitinib targets JAK1 and JAK3, whereas ruxolitinib inhibits JAK1 and JAK2. JAK inhibitors prevent the phosphorylation and activation of JAK, inhibiting dimerization and activation of STAT to move from the cell to the nucleus to influence DNA transcription and gene expression. Tofacitinib inhibits the expression of various interleukins, such as IL-16 and IL-23, thus suppressing Th17 differentiation. It also inhibits IL-15 expression, which increases keratinocyte apoptosis. Ruxolitinib suppresses the phosphorylation of STAT3, resulting in reduced expression of IFN-\gamma [72, 73]. Alantolactone, a sesquiterpene, is a STAT3 inhibitor that deactivates the STAT3 pathway and restricts the recruitment of immune cells [74].

4.12 Endogenous Peptide Hormones

\alpha-Melanocyte-stimulating hormone (\alpha-MSH) has anti-inflammatory properties. It downregulates inflammatory cytokines, such as IL-2/4/6/13 and TNF-\alpha, and upregulates the immunosuppressive cytokine IL-10 [75]. Likewise, the endogenous peptide diacerein, used in the treatment of osteoarthritis, inhibits the production of IL-1, IL-1\beta, IL-12, and TNF-\alpha, and is also a promising agent in the treatment of psoriasis [76]. Bilirubin is an endogenous antioxidant with anti-inflammatory activity. Bilirubin-loaded nanoparticles cross the stratum corneum and internalize into antigen-presenting cells (APCs) and keratinocytes, scavenging excess ROS and inhibiting IL-17-producing T cells [77].

4.13 RNA-Based Treatments

There is a change in the expression of various genes in psoriasis, and RNA-based treatments have been explored. RNA-based treatments are still in an investigational state. Although advances in delivery mechanisms and more targeted approaches have increased the interest in these treatments, they are still not widely approved or used in clinical practice for the treatment of psoriasis. Microinterfering RNAs (miRNAs) play vital roles in cell differentiation, proliferation, apoptosis, and immune responses. miRNA is highly expressed in psoriatic skin, and topical treatment with biomimetic reconstituted high-density lipoprotein nanogel of miRNA-210-antisense improved the psoriatic symptoms and reversed the immune disorder in the imiquimod-induced mouse model [24]. Similarly, elastic liposomal carriers of RNA interference (RNAi) downregulate human beta-defensin 2, a psoriasis marker, in a psoriatic tissue model [78]. Spherical nucleic acid nanoparticle conjugates (SNA-NCs) of short interfering RNA (siRNA) significantly reduce gene effects and cell proliferation [79].

4.14 Miscellaneous

Anthralin inhibits keratinocyte proliferation. It accumulates in the mitochondria and impairs the energy supply. It also interferes with DNA replication and slows cell division [80]. Tamoxifen, a selective estrogen receptor modulator, inhibits keratinocyte viability and induces an immune shift from Th1 to Th2. It releases anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. Squalene-integrated nanostructured lipid carriers increased the moisture and lipid content of the skin and reduced the Psoriasis Area and Severity Index (PASI) score and proinflammatory cytokine levels [81]. Leflunomide, a disease-modifying anti-rheumatic drug, exerts an antipsoriatic effect by slowing lymphocyte proliferation. Leflunomide rapidly metabolizes to teriflunomide and inhibits dihydroorotate dehydrogenase, a rate-limiting enzyme in pyrimidine synthesis in lymphocytes, thus modulating DNA synthesis [82]. Pentoxifylline is a hemorheological agent. It inhibits TNF-\alpha and suppresses IL-1, IFN-\gamma, Th1, and Th2 cells. Additionally, it acts as a vasodilator [83]. Ilomastat belongs to the hydroxamic acid category of reversible metallopeptidase inhibitors (RMIs). A curcumin-based ionic hydrogel loaded with ilomastat improved psoriatic skin lesions in mice by significantly reducing the expression of inflammatory cytokines, collagen-I, and metalloprotease 8 [84]. Fenoldopam mesylate is a highly selective dopamine receptor D1 agonist that is used in the treatment of hypertension. It is also effective in treating psoriasis because of its antiproliferative potential. It binds to dopamine receptor D1 of activated T cells and kills them while having a minimal effect on normal T cells. Glycerin-based carbopol gel of fenoldopam was effective in an imiquimod-induced mouse model [85, 86]. A comprehensive table summarizing drugs currently in clinical trials for psoriasis has been previously documented in the literature [26]. In this review, we provide a concise comparison of the key drugs available for psoriasis management, highlighting their mechanisms of action and effect in Table 1 (Ref. [20, 23, 24, 27, 28, 30, 33, 37, 38, 40, 42, 43, 45, 46, 49, 52, 64, 65, 66, 67, 72, 75, 77, 79, 80, 81, 82]).

5. Traditional Topical Formulations

Traditional topical formulations, such as creams, lotions, ointments, and gels, offer various benefits but have drawbacks. They may lead to itching, pain, inflammation, and local irritation and can be linked to erythema edema caused by drugs or excipients in the formulation [87]. Molecules with a small molecular weight can pass through the systemic circulation, which may be desired for the systemic delivery of therapeutic agents. However, when a local effect is required, the systemic absorption of the drug molecule may lead to undesirable side effects. For example, long-term use of super-potency corticosteroids may cause hypothalamus-pituitary-adrenal axis (HPA) suppression in young children [88]. Creams and ointments can be greasy, sticky, and have unpleasant odors. They may also be less effective and contain high drug concentrations, potentially affecting patient compliance. Creams, ointments, lotions, and gels exhibit imprecise and unpredictable drug delivery, and drugs do not remain at the site of action for the required period [89].

Nanotechnology plays an important role in overcoming the limitations of the conventional dosage forms. Nanocarriers increase the dermal retention of the drug, deliver the drug at the target site, and reduce the dose, thereby reducing side effects, and increasing patient compliance and acceptability [11]. Agarwal et al. [90] reported that the tolerability, efficacy, stability, and acceptability of liposomal gel formulations of dithranol increased in patients with plaque psoriasis compared to traditional cream formulations in an open-label trial. The co-delivery of clobetasol propionate and calcipotriol nanoemulsion loaded in the gel has high retention in the viable epidermis and dermis, negligible skin irritation despite high penetration, and controlled release, as reported by the authors [91]. These are just a few examples that demonstrate the added value of nanotechnology. Given their importance, the following sections provide a detailed overview of nano-based and other technical advances in drug delivery systems for the topical treatment of psoriasis.

6. Advances in Topical Drug Delivery Systems

Psoriasis is an immune-mediated skin condition that requires drugs targeting cells in the epidermis and dermis, including dendritic cells, Langerhans cells, keratinocytes, T lymphocytes, and mast cells. The stratum corneum of the skin is a barrier that limits drug entry to molecules 500 Da [92]. In psoriasis, increased epidermal thickness complicates drug delivery Nanocarriers address this challenge via intercellular, transcellular, or appendageal routes. They enhance skin hydration, modify drug properties, mimic skin lipid structures, and utilize permeation enhancers, facilitating drug penetration into deeper skin layers. Additionally, nanocarriers enable controlled and sustained drug release from the formulations [87]. A detailed discussion on nanotechnology-based delivery systems and the role of the physicochemical properties of nanocarriers in enhancing drug delivery is not included in this review, as it has been comprehensively addressed in other studies [6, 11, 93, 94, 95]. Unlike other reviews, this review adopts a comprehensive and integrative approach, focusing on both emerging therapeutic agents and nanotechnology-based drug delivery systems. While existing reviews have addressed the limitations of conventional therapies and provided broad overviews of topical or systemic treatments, this review uniquely emphasizes the integration of nanotechnology and emerging therapeutics, and the exploration of new therapeutic agents.

6.1 Vesicles

Liposomes are bi-layered vesicles of cholesterol, phospholipids, and fatty acids that encapsulate both hydrophilic and hydrophobic drugs. Liposome lipid composition enables drug delivery via skin. Lipid bilayer vesicles containing large concentrations of ethanol, known as ethosomes, increase permeation to deeper layers of the skin by opening new channels [25, 96]. Ethosomes containing anthralin demonstrated significantly superior results in enhancing the PASI, scoring 81.84% compared with liposomes (68.66%) in clinical trials involving patients with psoriasis [80]. Transferosomes, also known as deformable liposomes, have an aqueous core that is surrounded by lipids and amphiphilic surfactants. The elasticity of transferases is due to the presence of edge activators, along with phospholipids, which destabilize the lipid bilayer [97, 98]. Transethosomes have the combined properties of transferosomes and ethosomes, and are composed of phospholipids, edge activators, ethanol, and water. They can pass through the stratum corneum and enhance drug delivery to the dermis [25]. Rahangdale and Pandey prepared a topical transethosome formulation of the anti-inflammatory and PDE-4 inhibitor drug apremilast using sodium cholate, Lipiod S 100, and ethanol and incorporated it into 1% carbopol gel. An ex vivo permeation study on rat skin demonstrated that the drug penetrates the dermis layer where psoriasis originates, indicating its accessibility for therapeutic action [99]. Niosomes are non-ionic surfactant-based vesicular drug delivery systems. Niosomes are composed of an aqueous core surrounded by a surfactant macromolecule bilayer and cholesterol. Niosomes are osmotically active, less immunogenic, more stable, and less expensive [96]. Ceramide-based liposomes are known as cerosomes. These are composed of sphingolipids. Sphingolipids are natural lipids that make up 45–50% of the intercellular lipids of the stratum corneum and thus increase drug permeation and retention in the skin [100]. Lipospheres are lipid-based nanocarriers with a solid hydrophobic core surrounded by a phospholipid layer that acts as a stabilizer. Lipospheres are easy to prepare and have a low cost, stability, and high aqueous dispersibility. Lipospheres are favored for topical use in psoriasis because of their superior penetration across skin layers. Tacrolimus and curcumin-based liposomes reduced TNF-\alpha, IL-17, and IL-22 levels compared to those in the imiquimod group [101]. Thymoquinone in liposome formulations showed effective skin penetration and gradual drug release. In vivo, the results indicated substantial improvements in phenotypic and histopathological features, coupled with a significant decrease in IL-17 and TNF-\alpha levels in psoriatic skin compared to thymoquinone solution [102]. Cubosomes are bicontinuous cubic liquid crystalline systems composed of amphiphilic lipids, stabilizers, and water that can entrap hydrophilic, lipophilic, and amphiphilic drugs. Cubosomes have structural similarities to the skin, thus increasing the penetration of drug molecules. They can also retain moisture in the skin, providing additional benefits for psoriasis treatment [103]. Rapamycin, an immunosuppressant, was efficiently encapsulated in cubosomes using phytantriol, pluronic F127, ethanol, and water. The formulation exhibited a 95% encapsulation efficiency and sustained release for 14 days. Microneedles incorporating this formulation integrated into poly(vinylpyrrolidone) and poly (vinyl alcohol) demonstrated successful skin penetration and localized drug delivery in a skin-mimicking agarose gel. Rapamycin-loaded cubosome-like particles demonstrated antiproliferative effects on natural killer cells in vitro [104].

6.2 Nano and Microemulsions

Nanoemulsions are colloidal isotropic drug delivery systems, similar to regular emulsions. They have oil and aqueous phases as dispersed or continuous phases, stabilized by surfactants, but at low concentrations, and the size of droplets ranges from 20 to 500 nm. Microemulsions are similar to nanoemulsions, but the droplet size range is 5–100 nm, and they are thermodynamically stable [6, 96]. A cyclosporin microemulsion containing isopropyl myristate, Tween 80, and isopropyl alcohol was formulated to achieve droplet sizes below 50 nm. The local drug depot allowed sustained release of viable skin for 24 h. An ex vivo permeation study using goat skin demonstrated that a cyclosporine microemulsion gel significantly enhanced the permeability of cyclosporine compared with a traditional cyclosporine suspension [105].

6.3 Solid Lipid Nanoparticles (SLNs)/Nanostructure Lipid Carriers (NLCs)

SLNs, which are solid at body and room temperature, encapsulate hydrophilic and lipophilic drugs. They feature a lipid core stabilized by a surfactant, which enhances drug penetration through the stratum corneum. SLNs also increase contact with the skin, leading to enhanced skin hydration owing to their occlusive nature. The topical SLN formulation of retinoid acitretin showed an encapsulation efficiency of 89 \pm 1.8%, polydispersity index (PDI) of 0.488, and zeta potential of –17.2 mV. Aciterin-containing SLN in gel showed even skin distribution with 1.75 times more penetration than a drug in gel [106]. NLCs consist of liquid lipids embedded in solid lipids, offer a more lipid matrix, and have better encapsulation efficiency and stability. NLCs have better adhesion properties but low viscosity [25, 95]. Fluocinolone acetonide NLC, prepared via a modified microemulsion method, enhanced the in vitro drug distribution due to increased drug solubility in the lipid matrix, resulting in limited systemic distribution compared to a plain fluocinolone acetonide suspension [107].

6.4 Micelles

Micelles are colloidal drug delivery systems composed of self-assembled amphiphilic molecules with a core-shell structure above the critical micelle concentration (CMC). Micelles enclose hydrophobic drugs in a nonpolar core, and the polar shell faces the aqueous medium. The small size of micelles mediates crossing the stratum corneum and increases drug deposition in a viable layer of the skin [6, 108].

6.5 Dendrimers

Dendrimers are spheroidal, multivalent, hyperbranched, three-dimensional structures with active end groups. Dendrimers are biocompatible, increase the solubility of drugs, form prodrugs (drug-polymer conjugates), control the release of drugs, and increase the skin permeation of topically applied drugs [95].

6.6 Polymeric Carrier

Polymeric nanoparticles incorporate drugs into a polymeric matrix, releasing them through diffusion, erosion, or swelling. Microspheres (1–1000 µm) ensure controlled drug release, osmotically driven by polymer properties, drug amount, or drug-to-polymer ratio. Polymeric nanoparticles (10–100 nm) include nanospheres with dispersed drugs and nanocapsules with a core-shell structure for drug storage [98]. Coal tar-loaded PLGA nanoparticles exhibited a high drug loading of 92%, with a permeability study on the Strat-M membrane indicating 97% local drug accumulation within 24 h. The study also observed improved washability and reduced staining capacity of coal tar compared with crude coal tar [109].

6.7 Metallic Nanoparticles

Metallic nanoparticles are inert particles that are small in size and reactive against living cells [95]. Various metallic nanoparticles such as zinc oxide, silver, gold, and silica have been reported. They increase the permeation of drugs through the skin and exhibit anti-inflammatory properties [110, 111]. Methotrexate-loaded gold nanoparticles exhibited 70–80% loading efficiency, proved non-toxic to keratinocytes, demonstrated enhanced penetration in the epidermis and dermis of methotrexate from methotrexate-loaded gold nanoparticles compared to methotrexate alone, and displayed increased drug permeability through mouse skin [112].

6.8 Colloidal Carrier

Colloidal carriers offer many advantages such as high stability, high drug load, solubilization of poorly soluble drugs, and sustained release. Nanosponges (200–500 nm) can entrap hydrophobic and hydrophilic drugs and enhance cutaneous drug retention. Microsponges (size range 5–300 µm) provide prolonged contact time of the drug with the skin. It increases epidermal drug content while preventing absorption into the systemic circulation [113]. The microsponges of clobetasol propionate provide high encapsulation efficiency and a zero-order drug release pattern. In vivo drug efficacy research showed better antipsoriatic effects and reduced side effects compared to plain clobetasol propionate gel [114]. Cyclodextrin nanosponges of dithranol showed marked improvement in the antipsoriatic activity of the drug compared to the untreated group [115].

6.9 Microneedles

Microneedles, a non-invasive drug delivery system, penetrate the thick stratum corneum of the skin and enhance drug retention in the epidermis and dermis. Dissolvable microneedles improve drug delivery by dissolving them after their insertion into the skin [116]. Lu et al. [117] prepared a novel black phosphorus (BP)-loaded hydrogel inverse opal microneedle with photo and thermal responsive capability. The microneedle was composed of BP-loaded N-isopropyl acrylamide (NIPAM)/poly (ethylene glycol) diacrylate (PEGDA) inverse opal hydrogel scaffold and gelatin/agarose filled scaffold for drug loading. It was fabricated via nanoparticle assembly, and reversed-phase replication with micro-molding, which enables hydrophobic drug loading and photothermal responsive controlled drug delivery. This method enables good medication administration and efficiently improves psoriatic skin conditions by lowering the synthesis of inflammatory cytokines and epidermal hyperplasia in mice compared with calcipotriol ointment treatment. The dissolving microneedle array significantly increased the skin deposition of tofacitinib citrate (835 µg/cm²) compared with the control cream (143.98 µg/cm²) [73].

6.10 Technology-Assisted Drug Delivery

Various technical advances have also been explored to enhance drug delivery to the skin in psoriatic conditions. The increased epidermal thickness in psoriasis makes drug delivery via the topical route difficult, despite it being the preferred method for treating this condition. Skin pretreatment with a fractional laser using an Er: YAG laser device creates micropores and causes minimum coagulation, increasing drug penetration through the skin [67]. Iontophoresis uses a mild electric field to move a charged drug from the application site to the target site. The movement occurs because of electron repulsion or convection flow. Iontophoresis increases the transdermal penetration of drugs, depending on ionic strength [118]. Electroporation uses a high voltage of milliseconds to the skin to generate an electric pulse and create pores for transit time. Therefore, it increases drug transport due to electroosmosis and diffusion [119]. Recent clinical studies have shown that fractional CO₂ laser technology for the delivery of methotrexate is a promising, efficacious, and well-tolerated substitute for the conventional method of intralesional injection in the treatment of nail psoriasis [120, 121]. There was a significant improvement in the nail bed and Nail Psoriasis Severity Index (NAPSI) scores for combined fractional CO₂ laser and calcipotriol/betamethasone ointment preparation compared to fractional CO₂ laser alone in a clinical trial in 30 patients. NAPSI scores were calculated at the beginning of the study and 3 months after the last laser session. The patients received six laser sessions at 4-month intervals [122]. Wang et al. [119] proposed that there is a six-fold increase in the penetration of cyclosporin solution in 40% ethanol compared to passive diffusion using multiple pulse electroporation. Iontophoresis-assisted delivery can also effectively enhance the skin permeation of cyclosporin, particularly when combined with lecithin vesicles [123]. Table 2 (Ref. [42, 45, 50, 52, 55, 56, 58, 64, 65, 67, 68, 73, 74, 76, 77, 79, 80, 83, 90, 99, 107, 110, 113, 114, 119, 120, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188]) provides an overview of various nano-formulations of drugs used in psoriasis treatment. Detailed information on patented nanotechnology-based drug delivery systems can be found in existing literature.

The combination of innovative therapeutic agents with nanotechnology is transforming psoriasis management. It bridges the gap between drug innovation and effective delivery. By using advancements in nanotechnology, the limitations of conventional formulations, such as poor bioavailability, instability, and systemic side effects can be systematically addressed, paving the way for more effective treatment approaches.

7. Challenges and Limitations

Psoriasis is driven by complex immune system dysregulation, leading to inflammation and the rapid turnover of skin cells. Despite advancements in psoriasis treatment, several needs are still unmet. Traditional topical therapies may lead to poor skin penetration and retention, leading to suboptimal therapeutic outcomes. High costs and accessibility barriers also confine the widespread utilization of these advanced treatments.

Nanotechnology-based therapies are promising, but not without limitations. The industrial scale-up of nanoformulations is challenging due to complex manufacturing processes, regulatory challenges, and the need for precise quality control to ensure reproducibility and stability. Furthermore, the long-term safety and efficacy of nanoformulations require further clinical validation.

Finally, while natural agents and emerging drugs offer potential, their integration into scalable and clinically validated therapeutics still needs extensive research and development. For instance, biologics such as monoclonal antibodies that target specific components of the immune response (like TNF-\alpha inhibitors) have already transformed the management of moderate to severe psoriasis. However, these therapies are expensive and typically require systemic administration, which can lead to significant side effects. The development of cost-effective, patient-friendly solutions that balance efficacy, safety, and accessibility remains a critical goal for advancing psoriasis treatment.

8. Conclusion

Psoriasis is a chronic inflammatory skin condition that affects approximately 2–3% of the global population, posing significant challenges for both those affected and society as a whole. Although the specific mechanism involved in the development of psoriasis is still unclear, it mainly occurs due to abnormal differentiation and hyperproliferation of keratinocytes, leading to many structural and functional alterations in the skin. Conventional drug delivery systems provide insufficient skin penetration and retention and can also lead to systemic drug leaching. Therefore, nanoenabled drug delivery is required. With the increase in the understanding of the pathophysiology of psoriasis and various advances in nanotechnology-based drug delivery systems, it is possible to deliver the drug at the target site and enhance drug permeation and retention in the skin. The potential of many existing and new drug molecules is being explored, and various target sites are being identified. The exploration of both existing and novel drug molecules, along with the identification of new target sites, is underway and has shown potential. Combining possible therapeutic agents and nanotechnology could revolutionize the treatment of psoriasis, offering more efficient management and potentially shortening the treatment duration. Such advancements are likely to improve the quality of life of psoriasis patients. Future research should focus on developing disease-specific drugs and formulation techniques that can be scaled up to the industrial level while remaining safe, cost-effective, and providing more social benefits.

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Funding

Deanship of Research and Graduate Studies at King Khalid University(RGP2/580/45)