Abstract

Curcumin (CUR) has shown remarkable efficacy in the treatment of skin diseases, but its effective transdermal delivery is still a major challenge and stimulates interest in the design of novel systems for CUR dispersion, preservation, and delivery facilitation to the deeper layers of the skin. The present work aimed to investigate the potential of a nanohydrogel, formed by a micellar choline-calix[4]arene amphiphile (CALIX) and CUR, in the treatment of skin diseases through an imiquimod (IMQ)-induced psoriasis model. Psoriasis plaques are associated with aberrant keratinization, abnormal distribution of tight junctions (TJs) proteins, and enhanced expression of inflammatory markers. The nanohydrogel restored the normal distribution of TJs proteins ZO1 and occludin and reduced the expression of TNF-α and inducible nitric oxide synthetase (iNOS) compared to the untreated IMQ group. The novelty lies in the calix[4]arene-based nanohydrogel as a potential new soft material for the topical skin delivery of CUR. The nanohydrogel, due to its physicochemical and mechanical properties, enhances the drug water-solubility, preserves CUR from rapid degradation, and eases the local skin administration and penetration.

Highlights

  • The impact of psoriasis, as an inflammatory skin cell-mediated disease supported by a hyper-activation of cutaneous and immune cells, is remarkable on the world population, involving people of different ethnicities and ages [1]

  • Since the immune system plays a crucial role in the etiopathogenesis of psoriasis, we investigated t2h.4ro. uEgffehcttoofluHiyddirnoegebl lTureeastmtaeinntinong,MmasatsCt eclel lQl uinafnitlitfircaattiioonn, and degranulation [21]

  • BALB/c (6-week-old, male) mice were purchased from Envigo (Udine, Italy); IMQ topical cream was purchased from Aldara® 5% cream, Meda AB, Solna, Sweden; Sevofluorane 100% was purchase from Baxter (Rome, Italy); 10% neutral buffered formalin was obtained from Bio Optica (Milan, Italy); absolute ethanol was purchased from Carlo Erba (Milan, Italy); Hematoxylin and eosin were purchased from Bio Optica (Milan, Italy)

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Summary

Introduction

The impact of psoriasis, as an inflammatory skin cell-mediated disease supported by a hyper-activation of cutaneous and immune cells, is remarkable on the world population, involving people of different ethnicities and ages [1]. The therapeutic agents such as anti-inflammatory and immunomodulators are available for the treatment of psoriasis as topical or systemic therapy, but they have many side effects such as cutaneous atrophy and rebound of the disease. The anti-psoriasis effect of CUR can be related to different mechanisms of action including reduction of the oxidative stress and down-regulation of pro-inflammatory cytokines with consequent inhibition of nuclear factor NF-κB and enhancement of the skin barrier function [7,8]. The quantity of drug percutaneously absorbed is slowed down and diminished by the corneum stratum To overcome this drawback, nanotechnology is proving a promising strategy, and topical nanostructured drug delivery systems have been successfully developed for the treatment of skin diseases, including psoriasis [9]. Inflammatory markers, that are typical in psoriasis, like TNF-α, IL1β, and mast cell degranulation, as well as occludin and ZO-1 tight junctions (TJs), were examined

Results
Effect of Hydrogel Treatment on iNOS
Discussion
Materials and Methods
Animals
Anti-Psoriatic Efficacy
Experimental Groups
Histological Analysis
Toluidine Blue Staining
Western Blot Analysis
Materials
4.10. Statistical Analysis
Conclusions

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