Psoriasis is reported to be a widely spread autoimmune skin disease featuring high epidermal proliferation and increased dermal inflammation. Psoriatic skin lesions are mostly scaly, red, sharply detached and hardened plaques. Psoriasis affects about 3 % of the general population. Despite no age exemption, young and middle-aged adults represent the highest affected categories among psoriasis patients [1]. Psoriasis significantly impairs both the quality and expectancy of the affected patients’ lives. It may lead to depression and social stigma [2]. Also, psoriasis has been linked to cardiovascular diseases and lymphoma [3].

Psoriasis has a major genetic component, with heritability estimated to be 60–90 % [4]. However, it is thought that other factors like smoking, air pollutants, skin infections, alcohol, drugs and emotional stress could trigger the initiation of that torturing disease [1,2]. Also, oxidative stress is thought to contribute to the prognosis of psoriasis [1]. Plaque psoriasis and psoriasis vulgaris are the most frequent kinds of psoriasis. Additionally, psoriasis includes pustular, erythrodermic, inverse, guttate, scalp and nail psoriasis [3,5].

Psoriasis can be managed by topical, systemic medications or phototherapy depending on the severity of the disease [6]. Topical medications containing synthetic vitamin D3 analogues, corticosteroids, retinoid derivatives or anthralin may be utilized. On the other hand, systemic medications include calcineurin inhibitors, immunosuppressive medications, acitretin and isotretinoin.

Prolonged administration of systemic treatments is associated with several side effects [7] while the conventional topical delivery of anti-psoriatic agents with high doses may suffer from limited delivery to affected areas of skin along with skin irritation due to high local drug concentration [6].

Nanocarriers can overcome the limitations of conventional psoriasis treatment as they improve drug solubility, stability, bioavailability, and penetration through skin layers hence the pharmacological effects of drugs are improved [6]. Lipid-based nanocarriers can be used to achieve effective topical and transdermal drug delivery. They have low toxicity, better thermal stability compared with other types of nanocarriers and can be easily prepared on a large scale [6].

Among lipid-based nanocarriers are emulsomes (EMLs) which are lipid-based vesicles typically composed of a phospholipid bilayer surrounding a solid lipid core. It merges the advantages of both liposomes and nanoemulsions. The phospholipid bilayer aids in the stabilization of EMLs’ structure with no need for surfactant addition. The solid lipid core increases the solubilization of poorly soluble drugs, increases drugs’ loading efficiency and provides extended drug release [8].

Another approach to ensure effective drug delivery in psoriasis is the use of microneedle (MN) technology. A MN patch represents an array of arranged micron-size pointed projections [9]. MNs are a rapidly emerging drug delivery technology due to their potential to painlessly penetrate the skin and deliver compounds directly to the desired site [9]. Additionally, MNs showed high potential for prolonged and controlled delivery of drugs, effective transdermal and intradermal medication availability, the possibility of treatment cessation, providing high localized drug accumulation, reducing dosage regimen, overcoming needles’ phobia and providing non-invasive self-administration [10,11]. Thus, recently, researchers have explored the MNs’ applications for the delivery of tacrolimus [12] and calcipotriol [13] for the treatment of psoriasis as a promising therapeutic approach.

In particular, hollow MNs (Ho-MNs) are fabricated to have a central or off-central pore in their tip. Those holes act as direct micro-openings in the dermal layers permitting the drug to flow into the skin layers [14]. In turn, this modality would allow for steep drug diffusion and promote local drug concentration leading to superior localized pharmacological productiveness [10]. Ho-MNs are advantageously characterized by securing accurate adjustable doses and controlling drug delivery rates without restrictions on the drug formulation being administered [9,15]. For instance, considering psoriasis management, resin Ho-MNs proved highly efficient in delivering methotrexate to psoriatic skin successfully [16].

Leflunomide (LEF) belongs to disease-modifying antirheumatic drugs (DMARD) that can be used as a monotherapy in both psoriatic arthritis and rheumatoid arthritis treatment. Besides, LEF was proven to have a positive effect on psoriasis treatment. Post-marketing studies have revealed that treatment with LEF has pharmacological effects resembling those of methotrexate and superior to other DMARDs [17]. Kaltwasser et al. [18] reported that leflunomide has proven clinical efficacy in one hundred ninety patients having psoriatic arthritis and active psoriasis [18]. Also, Nash et al.[19] reported that leflunomide has manifested a promise in the therapeutic outcomes of human plaque psoriasis and psoriatic arthritis [19].

Teriflunomide (TER) (A77-1726) which is the active (LEF) metabolite can inhibit de novo pyrimidine synthesis due to selective inhibition of a dihydroorotase dehydrogenase [20]. TER leads the actively proliferating T cells and B lymphocytes to undergo cell cycle arrest through inhibition of clonal expansion. Besides, TER has anti-inflammatory and immunomodulatory properties that may be attributed to the reduction of nuclear factor KB-dependent gene transcription, tumor necrosis factor-induced nuclear factor KB activation, production of cell adhesion molecules, and protein kinases [21].

Prolonged systemic administration of LEF and its metabolite (TER) has been reported to cause several adverse effects including immune suppression, elevated liver enzyme levels, gastrointestinal symptoms and cytopenia [20,[22], [23], [24]].

The main aim of the current study is to present an effective minimally invasive method for psoriasis treatment with reduced side effects. To attain this, TER-loaded EMLs were prepared and in vitro, characterization of the prepared carriers was performed. The selected EMLs were administered to mice with an imiquimod-induced psoriasis model through a transdermal route using hollow MNs to ensure effective transdermal drug delivery.

To our knowledge, this is the first report for the administration of TER-loaded EMLs for psoriasis management through intradermal delivery using Ho-MNs.