Nanocarriers for Psoriasis Treatment: Insights from a Clinical Trial Registered on the Global Clinical Trials Registry Platform

Introduction

Psoriasis, a chronic immune-mediated inflammatory skin disease, is characterized by abnormal keratinocyte proliferation and immune cell infiltration into the dermis and epidermis, resulting in pruritic, scaly, and erythematous plaques on the skin.¹ This condition affects an estimated 2–4% of the global population.^1,2 Management strategies for psoriasis include topical therapy, systemic agents, and phototherapy, with treatment selection primarily determined by disease severity.^3,4 Topical medications are typically the first-line treatment for mild-to-moderate cases, whereas moderate-to-severe cases often require phototherapy or systemic therapy.⁴ Systemic therapy is frequently combined with topical treatments to enhance therapeutic outcomes.⁵ However, current therapeutic methods for psoriasis have notable shortcomings. Phototherapy is costly and prone to toxicities, such as photoaging, sunburn, and erythema.⁶ Although systemic drugs are efficacious in many cases, they often trigger adverse reactions, including nephrotoxicity, hypertension, hepatotoxicity, skin cancer, and hyperlipidemia.^7,8 Additionally, immunosuppressants and biologics with immunosuppressive properties, although effective for moderate-to-severe psoriasis, are limited by the heightened risk of infection and adverse cardiovascular and hepatic effects.^9,10 Consequently, topical treatments have emerged as the predominant choice for most patients, with nearly 80% selecting them as their primary therapeutic modality.⁵

In patients with psoriasis, atypical keratinocyte proliferation and differentiation in the epidermis not only increase skin stiffness and rigidity but also markedly decrease drug permeability.¹¹ This dysfunction of the skin barrier further increases transepidermal water loss and decreases hydration in patients with psoriasis, thereby exacerbating skin dryness and rigidity.¹² Consequently, topical traditional formulations exhibit notable limitations in addressing these pathological changes, including restricted drug penetration, increased dosing frequency, adverse toxicological reactions, and reduced patient compliance.¹³

Nanocarriers are recognized for their ability to enhance drug penetration and overcome the skin barrier; consequently, their potential for treating skin diseases has been widely recognized.^14,15 The active pharmaceutical ingredients (APIs) encapsulated within nanocarriers can traverse different skin strata through multiple pathways, including transcellular, intercellular, and transappendageal routes.¹⁴ The mechanism of skin penetration is markedly influenced by the physicochemical characteristics of both the active drug and its carrier, including particle size, charge, mobility, and the balance of hydrophilic and lipophilic.¹⁴ Among the critical parameters for follicular targeting, the particle size and mobility of nanocarriers in targeted drug delivery are paramount.^16,17 Compared with conventional topical formulations, nanocarriers can substantially reduce the required API dose to achieve therapeutic efficacy, thereby mitigating the adverse effects associated with traditional treatments, enhancing drug solubility and bioavailability, and minimizing toxicity.^18,19

Several studies^20–22 have comprehensively reviewed nanocarrier-based strategies for psoriasis therapy, including liposomes, niosomes, ethosomes, solid lipid nanoparticles, nanoemulsions, and transferosomes. However, these reviews primarily focus on formulation strategies, physicochemical characterization, and therapeutic efficacy in preclinical animal models, providing limited insight into advances in clinical application. Clinical trials are a pivotal phase of drug development, serving as the primary means of validating safety and efficacy in humans.^23–25 Well-designed clinical trials are essential for successful drug development, as their quality directly influences the efficiency of translational processes and the likelihood of regulatory approval and market entry.^26,27 Consequently, a systematic analysis of registered clinical trial data is essential for informing clinical practices and guiding future research. A narrative synthesis of the characteristics of registered trials can yield valuable information regarding clinical trial design trends and the potential market prospects of emerging therapies.²⁸ In this study, we conducted a comprehensive search of major clinical trial databases, including the ClinicalTrials.gov database and the International Clinical Trials Registry Platform (ICTRP), with a specific focus on topical nanocarriers for psoriasis treatment. Based on the identified studies, a narrative review was conducted to analyze the key trial characteristics and evaluate the advantages of different nanocarrier categories.

Methodology

This study used ClinicalTrials.gov (https://clinicaltrials.gov/) and the ICTRP (https://trialsearch.who.int/) to conduct a systematic search for clinical trials of nanocarrier-based psoriasis treatments. The search strategy included two terms: “psoriasis” and “liposome or nanoparticle or nanoformulation or niosomes or ethosom or nanosphere or nanocapsule or nano*”. All other parameters were set to default values. After removing duplicate entries, the studies were manually screened using the following inclusion criteria: interventional study design, psoriasis as the target condition, and drug delivery via nanocarriers. Studies were excluded if they were non-interventional or if the condition addressed was not psoriasis. Subsequently, the included studies were analyzed using the “Trial ID” as the primary identifier. To further identify relevant studies, a comprehensive search was conducted in PubMed, Web of Science, Embase, Ovid MEDLINE(R), and Cochrane databases.

Results

Screening and Included Trials

On September 21, 2025, a search of the ClinicalTrials.gov and ICTRP databases identified 5,338 randomized controlled trials (RCTs) involving psoriasis treatment. Employing nanocarriers as the screening criterion, including liposomes, nanoparticles, nanoformulations, niosomes, ethosomes, nanospheres, nanocapsules, and all terms prefixed with “nano”, 57 RCTs involving nanocarriers for psoriasis treatment were initially selected. Following a thorough verification process, 46 studies that did not meet the criteria for nanocarrier-based psoriasis treatment were excluded. One RCT (NCT03004339) was excluded because the submicron particle paclitaxel investigated was an uncoated nanoparticle paclitaxel produced via supercritical carbon dioxide technology, which did not meet the definition of a nanoformulation. Consequently, 11 RCTs were included in this review. Figure 1 presents a flowchart of this study.

Figure 1 Flow diagram of the study. Abbreviation: ICTRP, International Clinical Trials Registry Platform.

Characteristics of the Included Studies

A time-series analysis of the 11 included RCTs revealed an accelerating trend in the investigation of nanocarriers for psoriasis treatment. Following a period of minimal and stable trial initiation from 2000 to 2015 (9% per five-year interval), research activity increased markedly since 2016. This surge is particularly evident during the 2021–2025 period, which accounts for 45% of trials, indicating a recent and substantial intensification of research focus in this domain.

The geographical distribution of these studies was markedly concentrated, with Iran and China emerging as the predominant applicant countries for trial initiation (27% each), followed by Egypt (18%). ClinicalTrials.gov is the primary registry, encompassing 45% of these trials. Concerning trial progression, the largest proportion of studies (45%) is currently in the “Not Recruiting” phase, a percentage considerably higher than those that are completed (27%) or actively recruiting (18%). For further details, see Figure 2.

Figure 2 General characteristics of the included studies. Abbreviations: IRCT, Iranian Clinical Trials Registry; ChiCTR, Chinese Clinical Trial Registry; CTRI, Indian Clinical Trials Registry.

Type of Nanocarriers and Active Pharmaceutical Ingredients

Six types of nanocarriers were identified in the 11 RCTs: microemulsion/nanoemulsion (4 RCTs), chitosan nanoparticles (3 RCTs), liposomes (2 RCTs), ethosomes (1 RCT), micelles (1 RCT), and niosomes (1 RCT). Notably, one RCT (NCT03348462) incorporated two types of nanocarriers: ethosomes and liposomes. Regarding the physicochemical properties of the active pharmaceutical ingredients (APIs) used in these RCTs, six RCTs involved lipophilic drugs with Log P > 0; one RCT used a hydrophilic drug; one RCT used a plant/plant extract; and three RCTs employed traditional Chinese medicine. For details, see Table 1.

Table 1 Type of Nanocarriers and Active Pharmaceutical Ingredients

Design Characteristics of the Included Clinical Trials

Among the 11 RCTs, the clinical design imposed no sex restrictions, with treatment as the primary objective. Eight RCTs were restricted to adults, whereas the remaining three RCTs had no age restrictions. According to the established criteria for high-quality clinical trial design, namely randomization, appropriate blinding, parallel group structure, and adequate sample size determination,^30–32 one RCT (NCT00006276) was of low quality, classified as Phase 2, and featured an open-label design, with the allocation and intervention model not reported. In contrast, the remaining 10 RCTs met the criteria for high-quality design. Regarding allocation, nine RCTs were randomized, whereas 1 RCT was not. Regarding the intervention models, 10 RCTs employed a parallel design. In terms of masking, 5 RCTs were double-blinded, 4 RCTs were open-label, and 1 RCT was single-blinded. For further details, see Figure 3.

Figure 3 Design characteristics of the included clinical trials.

Primary Outcomes of the Included Trials

Among the 11 identified RCTs, five reported complete or partial outcome data. Table 2 summarizes the demographic characteristics of the enrolled participants and the primary outcomes of these trials. The participants were predominantly middle-aged, with mean ages ranging from approximately 36 to 46 years in most studies. However, the evidence base was limited by small sample sizes: only one trial (NCT00438360) enrolled more than 100 participants (160 vs 79) over 24 weeks, whereas the remaining four RCTs enrolled fewer than 50 participants. The interventions primarily involved topical drugs (four RCTs), with only one oral drug. The Psoriasis Area and Severity Index (PASI) was the principal efficacy endpoint across the studies. However, baseline and follow-up PASI data were incompletely reported in some trials. For example, the cyclosporine A microemulsion trial did not report the baseline PASI, and the curcumin niosome gel trial did not report PASI outcomes. Among trials with comparable reporting, formulations combining an active agent with a nanocarrier generally demonstrated greater PASI improvement than those with blank nanocarriers. Specifically, turmeric microemulgel reduced PASI from 3.6 to 1.4 over 9 weeks, whereas the blank nanocarrier group showed minimal change (3.7 to 3.2). Similarly, nano-modified Runji ointment reduced PASI from 23.84 ± 4.94 to 6.42 ± 4.13 in 8 weeks, exceeding the improvement observed with the blank nanocarrier (24.06 ± 5.56 to 11.06 ± 4.81). These findings suggest that nanocarrier-based topical delivery systems may decrease the severity of psoriasis. However, the strength of inference is constrained by several limitations, including small sample sizes, heterogeneity in treatment duration, baseline disease severity, and incomplete outcome reporting. Consequently, larger, rigorously designed RCTs with standardized and comprehensive PASI reporting are necessary to confirm these preliminary indications of benefit.

Table 2 Demographic Information of the Patients and Primary Outcomes of the Included Trials

Discussion

Advantages of Nanocarriers for Psoriasis Treatment

The present study identified the nanocarriers employed in RCTs for psoriasis treatment, including microemulsions/nanoemulsions, chitosan nanoparticles, liposomes, ethosomes, micelles, and niosomes. The structures of these nanocarriers are illustrated in Figure 4. Compared to traditional formulations, nanocarriers provide numerous advantages, including enhanced solubility, bioavailability, targeted drug delivery, controlled release, and reduced toxicity.^36,37 Nanocarriers have been widely investigated for the treatment of skin diseases.^5,38 Distinct nanocarriers exhibit unique advantages and disadvantages; hence, the choice of an appropriate nanocarrier must be determined by the therapeutic aim and the drug’s physicochemical properties during the design phase.³⁹ Additionally, nanocarrier design should incorporate key physicochemical characteristics, including size, shape, surface chemistry, porosity, and flexibility, as these parameters significantly govern their biological behavior and interactions with biological barriers.³⁹ Table 3 outlines the primary advantages and disadvantages of nanocarriers used in RCTs for psoriasis treatment.

Table 3 The Main Advantages and Disadvantages of Nanocarriers Used in RCTs for Psoriasis Treatment

Figure 4 Types of nanocarriers used for drug delivery in psoriasis treatment. (A) micro/nanoemulsion; (B) micelles; (C) chitosan nanoparticles; (D) liposomes; (E) ethosomes; (F) niosomes.

Characteristics of the Active Pharmaceutical Ingredients

Of the 11 RCTs, the active pharmaceutical ingredients (APIs) employed in the interventions were classified mainly into three categories: lipophilic drugs (Paclitaxel, Cyclosporine, Anthralin, Curcumin), hydrophilic drugs (Methotrexate), and botanical agents (Boswellia, Qinteng Huoxue Runji Ointment, Runji Ointment). Owing to their favorable skin permeability, lipophilic APIs generally demonstrate superior efficacy in topical formulations.⁴⁸ In contrast, hydrophilic APIs such as Methotrexate are primarily indicated for systemic administration.⁵² Although Methotrexate is effective against psoriasis, prolonged use may lead to adverse events, including hepatotoxicity.⁵³ These data are consistent with the findings of the current study. Only one RCT in this analysis employed a hydrophilic API.

When designing and applying nanocarriers for psoriasis treatment, the physicochemical properties of APIs should be carefully considered. First, transdermal drug delivery for psoriasis is considerably more challenging than for non-keratotic skin disorders. This is attributed to the intrinsic barrier function of the skin, which limits drug penetration,⁵⁴ and to the pathological features of psoriatic skin, including hyperproliferation, hyperkeratosis, and reduced hydration, which further hinder API permeation and exacerbate therapeutic limitations.^54,55 Moreover, the molecular weight and partition coefficient of APIs significantly influence the self-assembly and physicochemical characteristics of nanocarriers, which in turn affect their penetration efficiency and biodistribution.^56,57 Therefore, a careful consideration of API properties is essential for the selection and rational design of nanocarriers to achieve optimal therapeutic outcomes.

Challenges in Regulatory Frameworks

Our study revealed that the proportion of registered RCTs focusing on nanocarriers for psoriasis treatment is notably limited, comprising only 0.2% (11 of 5,338) of all registered RCTs for psoriasis intervention. This observation highlights the significant paucity of clinical investigations directly involving human subjects, as most existing research employs animal models or cell lines to replicate experimental conditions.⁴²

Nanocarriers are used in the topical treatment of dermatological conditions; however, they are challenged by incomplete regulatory frameworks. US The Food and Drug Administration (FDA), European Medicines Agency (EMA), and Chinese Food and Drug Administration (CFDA) have not issued guidance on the use of topical nanocarriers. Moreover, the regulatory frameworks for nanomedicines vary across countries. The FDA has not established regulatory definitions for “nanotechnology”, “nanomaterial”, “nanoscale”, or other related terms. Instead, it continues to utilize the considerations proposed in 2014. A drug product or material was defined as nanoscale if its particle size is within 1–100 nm or if it exhibits size-dependent physical, chemical, or biological properties, even if its size may extend beyond the nanoscale to the micrometer range (1000 nm).^58,59 The EMA defines nanotechnology as follows: “Nanotechnology is defined as the production and application of structures, devices, and systems by controlling the shape and size of materials at the nanometer scale. The nanometer scale ranges from the atomic level at approximately 0.2 nm (2 Å) to approximately 100 nm”.⁶⁰ The CFDA characterizes nanomedicine as nanoparticles synthesized through nanotechnology or as nanoparticles resulting from combining raw pharmaceuticals with suitable carrier materials, including final drug formulations. The external dimensions, internal configuration, and surface architecture of the final product or carrier material in nanomedicine are at the nanoscale, specifically 100 nm or smaller. Alternatively, the particle size of the final product or carrier material generally remains below 1000 nm, and these entities demonstrate notable size-dependent effects.⁶¹

Challenges in Large-Scale Production and Long-Term Stability

Large-scale production and long-term stability remain significant challenges in the translational development of nanocarriers. In particular, the scalability and reproducibility of nanocarrier formulations pose substantial technical hurdles, as maintaining physicochemical stability, structural uniformity, and consistent drug-loading capacity under industrial manufacturing conditions is challenging. One contributing factor is the wide variety of polymeric materials used in nanocarrier preparation, which can substantially influence the formulation’s uniformity and overall quality. Moreover, the absence of standardized manufacturing protocols further exacerbates these challenges. Different research groups often employ distinct preparation methods, leading to considerable variability in nanocarrier size, morphology, surface characteristics, and drug loading efficiency.^62,63 This lack of standardization complicates cross-study comparisons and undermines the reproducibility required for large-scale production. Consequently, the development of advanced manufacturing equipment and platforms with robust scale-up capabilities has become a significant focus in nanomedicine, aiming to facilitate the reliable and consistent industrial production of nanocarrier-based formulations.⁶⁴

Nanocarriers possess a large specific surface area and are therefore highly susceptible to aggregation, precipitation, and degradation under various environmental conditions,^65,66 which may lead to the deterioration or complete loss of their nanoscale properties.^67,68 Consequently, effective strategies are required to enhance nanocarrier stability during storage. A commonly employed approach to improve the storage stability of nanoparticles involves the use of cryoprotectants, particularly at low temperatures. For example, Zhao et al 56 demonstrated that nanoparticles loaded with mRNA retained their delivery efficiency for at least three months when cryoprotectants were applied during freezing or lyophilization and the formulations were stored in liquid nitrogen.

Challenges in Potential Toxicity

The potential toxicity of nanocarriers is another major challenge in the development of nanomedicine. Evidence suggests that smaller nanoparticles are associated with increased toxicity, enhanced chemical reactivity, and heightened biological activity.^69,70 Following systemic exposure, nanocarriers may accumulate within the organ phagocytic system, where they can exert toxic effects on organs such as the liver, spleen, and kidneys.⁷¹ Significantly, nanocarrier toxicity is strongly influenced by the route of administration, level, and duration of exposure.⁷² Although the transdermal delivery of nanocarriers is generally considered safer than oral or injectable administration,⁷³ their potential long-term toxicity cannot be disregarded. Notably, there remains a significant knowledge gap regarding the chronic and cumulative effects of persistent nanocarriers, leading some researchers to propose that they should be regarded as “potentially hazardous” and handled with caution.⁷⁴

From a pharmacokinetic perspective, APIs can penetrate the skin via multiple pathways, including transcellular and intercellular routes. Skin penetration is strongly governed by the physicochemical properties of both APIs and their associated nanocarriers, such as particle size, surface charge, mobility, and the balance of hydrophilicity and lipophilicity.¹⁴ In this context, the use of biocompatible and biodegradable polymeric materials represents a promising strategy for designing safer nanocarriers.

Limitations and Future Perspective

The present study had two primary limitations. First, the number of included RCTs was limited, which may constrain the generalizability and robustness of our findings. Second, as a narrative review, this study did not conduct a systematic assessment of the risk of bias in the included studies, nor did it integrate such evaluations into the overall synthesis, which may have affected the rigor and reliability of its conclusions.

This review focuses on the design characteristics and clinical applications of RCTs involving nanocarriers for psoriasis treatment. Future studies should adopt a broader perspective by systematically examining the design characteristics of RCTs investigating nanocarriers for transdermal delivery systems across a wide range of diseases, thereby providing robust evidence to support the evaluation of the safety and therapeutic efficacy of topical nanocarriers. Particular attention should be paid to clinical trial design considerations and to the risks of nanomedicine use in the context of potential tissue injuries. Finally, interdisciplinary collaboration among materials scientists, pharmacologists, and dermatologists is strongly advocated, as integrative efforts can foster innovative approaches and accelerate the clinical translation of nanocarrier-based therapies for psoriasis.

Conclusion

Nanocarriers are a promising alternative to conventional drug therapies owing to their ability to enhance the delivery of active pharmaceutical ingredients (APIs) to the skin layers via interactions with skin lipids, thereby increasing transdermal penetration. However, the clinical application of nanocarriers in psoriasis treatment faces numerous challenges, including inadequate regulatory frameworks, difficulties in large-scale production, and issues related to long-term stability. Consequently, only 0.2% of registered RCTs on psoriasis treatment focus on nanocarrier-based therapies. Moreover, existing studies have not directly compared nano- and non-nano formulations. Because nanomedicines differ fundamentally from conventional preparations, a rigorous clinical design necessitates the incorporation of three parallel arms: blank nanocarriers, conventional formulations, and nanoformulations. Therefore, future research should focus on overcoming these translational barriers by optimizing nanocarrier stability, developing robust and scalable production methods, and conducting thorough, long-term safety evaluations. This strategy is essential for bridging the gap between laboratory potential and clinical application.