Background
Psoriasis is a common chronic inflammatory skin disease. Its treatment is challenged by the limited amount of drug reaching the inflamed skin. The overexpressed CD44 protein in inflamed psoriatic skin can serve as a potential target of novel active-targeting nanocarriers to increase drug accumulation in the skin.
Conclusion
We demonstrated increased topical drug delivery of curcumin to inflamed tissues using HA-ES targeting the highly expressed CD44 protein. This innovative strategy could be applied for the development of topical drug delivery systems targeting inflamed skin.
Methods
Hyaluronic acid (HA) was linked to propylene glycol-based ethosomes by covalent binding to develop a novel topical drug delivery carrier (HA-ES) for curcumin. An imiquimod-induced psoriasis mouse model was established, and curcumin delivery and anti-psoriatic efficacy using HA-ES were compared with those using plain ethosomes (ES).
Results
The HA gel network formed on the surface of HA-ES reduced the leakage and release of poorly water-soluble curcumin. Compared with ES, transdermal curcumin delivery was significantly enhanced by using HA-ES as vehicles; the cumulative transdermal amount and the amount retained in the skin in vitro after 8 h were, respectively, 1.6 and 1.4 times those observed with ES, as well as 3.1 and 3.3 times those observed with a curcumin propylene glycol solution (PGS), respectively. The in vivo psoriatic skin retention of curcumin with HA-ES was 2.3 and 4.0 times that of ES and PGS, respectively. CD44 expression in imiquimod-induced psoriasis-like inflamed skin was 2.7 times that in normal skin. Immunostaining revealed similar results, suggesting that the specific adhesion of HA-ES to CD44 increased drug accumulation in the skin. After topical administration to mice, the HA-ES group showed an alleviation of inflammation symptoms; lower TNF-α, IL-17A, IL-17F, IL-22, and IL-1β mRNA levels; and lower CCR6 protein expression compared to the ES and PGS groups.