Background: The high surface-to-volume ratio, tiny size, general non-toxicity, and ease of functionalization of nanostructured lipid carriers make them an excellent option for topical drug delivery systems.

Methods: The NLC of Bergenia crassifolia extract composed of soy wax as a solid lipid and Sea buckthorn seed oil were prepared using the hot melt method and embedded in a topical gel. The Box–Behnken experimental design was run and the gels were prepared using 1% carbopol-934. The characterization of NLC and nanogels was carried out using bergenin as a biomarker. A mouse model of imiquimod-induced psoriasis was used to carry out our in vivo study.

Results: The characterization of NLC showed the encapsulation of the extract. Studies on histopathology showed that the produced nanogel had a potentially effective anti-psoriatic effect. The findings indicated that, in comparison to plane extract gel, nanogel demonstrated anti-psoriatic action in a shorter amount of time. Additionally, the nanogel showed prolonged drug release for 12 hours and decreased the inflammatory markers IL-23 and IL-17 associated with psoriasis.

Conclusion: Nanogel improves penetration, deposits drugs deeper into the skin layers, and reduces systemic absorption compared to extracts, highlighting the potential of nanosizing to enhance biological activities. Dermatokinetics and preclinical findings show the downregulation of inflammatory mediators IL-23 and IL-17. The skin irritation study score indicated that the gel was not irritating. The results show that the nanogel is an effective and safe carrier for plant extracts. Clinical studies are needed to evaluate the efficacy of this treatment as an alternative or supplement to conventional treatments for psoriasis.