Layered double hydroxide Pickering emulsion with enhanced skin penetration and photostability for psoriasis treatment

Purpose: Psoriasis, a globally prevalent chronic skin condition affecting 2–5% of the world’s population, significantly deteriorates patients’ quality of life. Psoriasis is an immune-mediated skin disorder triggered by abnormal activation of keratinocytes in the epidermis, leading to excessive skin cell turnover. Local therapies serve as the cornerstone of psoriasis treatment, ranging from mild to severe cases. Despite efforts in drug development, patient satisfaction remains limited. Most psoriasis treatments encounter challenges in local delivery due to their low solubility and stability. Methods: To overcome these challenges, we developed a thymoquinone (TQ)-loaded oil-in-water layered double hydroxide (LDH) nanosheet Pickering emulsion (TLE) using exfoliated LDH nanosheets (LDH NSs), oleyl alcohol, and TQ. TQ, a naturally derived anti-inflammatory agent, was employed for the treatment of psoriasis. LDH NSs were used as emulsifiers for oleyl alcohol instead of traditional surfactants to produce Pickering-style emulsions. Results: In in vitro cadaver skin penetration experiments, the Pickering structure LDH emulsion (LE) accumulated in the stratum corneum and subsequently released the drug into the dermal layer. Additionally, owing to the inherent UV-shielding properties of LDH, TLE exhibited enhanced photostability when TQ was encapsulated within LDH oil droplets. Compared with the TQ-loaded polysorbate emulsion, TLE demonstrated 20.5% greater TQ absorption after solar irradiation, indicating the superior photostability of LE. Upon the application of TLE in an imiquimod-induced psoriatic mouse model, significant therapeutic effects were observed without any adverse side effects. Conclusion: This study demonstrated the excellent efficacy of LE derived from enhanced skin penetration, suggesting its potential as a transdermal drug delivery platform for various conditions.