CD44 Assists the Topical Anti-Psoriatic Efficacy of Curcumin-Loaded Hyaluronan-Modified Ethosomes: A New Strategy for Clustering Drug in Inflammatory Skin

Abstract

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.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.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.

Mechanistic Evaluation of Enhanced Curcumin Delivery through Human Skin In Vitro from Optimised Nanoemulsion Formulations Fabricated with Different Penetration Enhancers

“…The results of the experiments, including in vitro human epidermal permeation and stratum corneum solubility, were used to provide a mechanistic evaluation of the effect of the NE-based formulations on cutaneous delivery of curcumin. Recent work has begun to examine the efficacy of curcumin in treating skin disease [26], including the targeting of curcumin to specific cell populations in skin regions where diseases such as psoriasis [27] originate, as well as improved NE formulations for skin delivery of curcumin [28]. Results of our work will provide further mechanistic insights to enable us to design optimised delivery systems for cutaneous curcumin delivery.…”

Nanodermatology‐based solutions for psoriasis: State‐of‐the art and future prospects

“…Furthemore, Zhang and colleagues linked hyaluronic acid (HA) to ethosomes curcumin loaded in order to target CD44, a HA receptor overexpressed in psoriatic skin. Its application on Male C57BL/6 mice determine a statistically significant decrease in erythema and thickness together with a decreased mRNA levels of TNF‐α, IL‐17A, IL‐17F, IL‐22, and IL‐1β, confirming its antipsoriatic properties further enhanced by HA‐ethosomes (Zhang et al, ).…”

Solubility and Bioavailability Enhancement of Oridonin: A Review

“…Liposomes are microcapsules (Figure 7b) that can encapsulate both hydrophilic and hydrophobic drugs [109]. Commonly designed for targeted delivery or lymphatic orientation, liposomes can be administered in various routes, such as intravenous injection [110], oral administration [111], intraocular administration [112], pulmonary administration [113] and external use (including skin administration) [114] according to clinical needs. With the drug encapsulated in the lipid-like bilayer, the stability of the drug is enhanced by minimizing excretion and metabolism in a sustained release manner, which conduces to reduce the toxicity of the drug [115].…”