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Tapinarof-loaded nanogels significantly enhance skin penetration, stability, and anti-psoriatic efficacy, offering a safe, steroid-free topical treatment for long-term psoriasis management.
A novel review by researchers at the University of Debrecen highlights tapinarof nanogels as a groundbreaking alternative for treating psoriasis—a chronic, immune-mediated skin disease affecting over 100 million people globally. Published in Pharmaceutics, the review emphasizes how nanogel-based delivery systems markedly enhance tapinarof’s effectiveness by improving skin penetration, stability, and tolerability.
While conventional therapies, including corticosteroids and biologics, provide relief, they are often linked with adverse effects, high costs, or poor patient adherence. Tapinarof, a newly FDA-approved topical aryl hydrocarbon receptor (AhR) agonist, has emerged as a promising non-steroidal agent with anti-inflammatory, antioxidant, and skin barrier-restoring effects. It modulates cytokines such as interleukin (IL)-17 and IL-22, activates the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway, and enhances the expression of barrier proteins like filaggrin and loricrin.
However, its poor water solubility and instability under environmental stress have restricted its delivery in conventional formulations. To overcome these challenges, the research team developed tapinarof-loaded nanogels using Carbopol 940 and 936 polymers, alongside excipients like Tween 80, Kolliphor, and oleic acid. These nanogels illustrated favorable properties for topical application: particle sizes ranged from 151 to 173 nm, rheological testing confirmed pseudoplastic flow suitable for skin application, and texture analysis indicated low compressive resistance, making the formulation easy to spread.
Cytotoxicity testing on HaCaT (Human adult low Calcium high Temperature) keratinocyte cells illustrated no harmful effects, confirming good skin tolerability. Importantly, Franz diffusion studies revealed a superior release profile in nanogel II, where 81% of tapinarof was released within 5 hours, compared to 52% in nanogel I. The nanogels also improved wound healing in vitro by boosting antiproliferative and antimigratory effects. Clinically, tapinarof has already shown robust efficiency and safety. In phase II trials involving 227 adults battling plaque psoriasis, up to 65% of those using 1% tapinarof twice daily attained a “clear” or “almost clear” rating on the Physician Global Assessment (PGA), compared to 11% in the placebo group. Psoriasis Area and Severity Index (PASI)-75 response rates reached 46–65%.
In two large phase III trials (PSOARING 1 and 2), involving over 1,000 patients, 35–40% achieved a clear or almost clear PGA score, and PASI-75 responses ranged from 36–48% after 12 weeks of once-daily application. The PSOARING 3 long-term extension study (n=763) found that 40.9% of patients achieved full skin clearance at least once, with benefits lasting up to 4 months after stopping treatment. Common side effects included folliculitis, contact dermatitis, and mild upper respiratory symptoms, but the majority of reactions were mild and non-disruptive.
Tapinarof’s therapeutic efficacy is rooted in its ability to activate AhR signaling pathways, decrease Th17 cytokine production, restore skin barrier function, and suppress oxidative stress. Unlike resveratrol, a plant-derived stilbene, tapinarof (produced by the bacterium Photorhabdus luminescens) is more potent and selective in AhR activation, leading to pronounced immunomodulatory effects. With its antimicrobial and antioxidant properties, tapinarof is now being inspected beyond psoriasis—for example, in atopic dermatitis and ophthalmic diseases. However, its formulation remains a technical hurdle due to its hydrophobicity and susceptibility to degradation.
Nanogels offer an effective solution to these limitations by boosting tapinarof’s solubility, stability, and skin penetration while allowing controlled and prolonged release. They also support hydration, improve patient comfort, and may boost adherence, especially vital for chronic ailments like psoriasis. Compared to conventional creams and ointments, nanogels hold remarkable advantages in delivering poorly soluble drugs, minimizing systemic absorption, and enabling localised action with fewer side effects. The researchers propose that tapinarof nanogels could be scaled up for clinical use following successful in vivo testing, including animal models like imikimod-induced psoriasis.
Additional phase I trials in healthy volunteers and safety studies in children, pregnant patients, and those using combination therapies are needed to validate widespread applicability. To sum up, nanogel-based delivery of tapinarof appears to be a game-changing advancement in topical psoriasis care, combining scientific innovation with improved therapeutic outcomes. It promises a steroid-free, effective, and patient-friendly solution, capable of addressing both the clinical complexity of psoriasis and the unmet requisition for safer long-term treatments.
Pharmaceutics
Tapinarof Nanogels as a Promising Therapeutic Approach
Barbara Balogh et al.
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