Piceatannol loaded mesenchymal stem cells derived exosomes for cutaneous regenerative treatment of psoriasis-like symptoms in imiquimod-induced mice model: Exosomal hydrogel impact via targeting of JAK3/STAT3 signaling.

The chronic failure of psoriasis treatment strongly recommends a tailored biocompatible therapeutic platform considering the immunological and inflammatory factors of psoriasis pathogenesis. This strategy recommends the utilization of natural phytomolecule of piceatannol due to its healing cutaneous potential, mesenchymal Stem cell-derived exosomes as a regenerative natural nanocarriers and a hydrogel facilitating prolonged release. This work aimed to augment the anti-psoriatic pattern of piceatannol utilizing the mesenchymal stem cells derived exosomes via topical delivery to imiquimod-induced psoriatic mice skin. The formulated exosomal piceatannol platforms were assayed for particle size analysis, entrapment efficiency, flow cytometry analysis, functional size of 137.6 nm, zeta potential of -61.4 ± 6.04 mV, PDI of 0.331, >97% positive expression of all the three tetraspanin markers (CD9, CD63, CD81), entrapment efficiency of 32.8 ± 1.7%, prolonged cumulative release reaching 37.5% after 72 h and satisfactory characterization of 2% w/w carboxymethylcellulose hydrogel. In vivo experimental estimation of the anti-psoriatic activity was conducted and supported by molecular analysis of IL-17, TNF-α, and pSTAT3 levels. mRNA expression of JAK3 was analyzed to explore the targeting of Janus kinase/STAT3. The findings revealed the promising anti-psoriatic activity of the exosomal piceatannol, supported by molecular potential in reducing the mentioned cytokine levels, targeting of JAK/STAT3 pathway and histopathological healing pattern in the psoriasis-induced skin. In conclusion, piceatannol was successfully shown to have a promising regenerative anti-psoriatic profile when loaded as an exosomal hydrogel.