Advances in antioxidant phytochemical for inflammatory skin diseases: mangiferin and naringin nanocarriers based lipids

Chronic inflammatory skin diseases are the most common topical disorders and the fourth cause of global disability. Among all, psoriasis (PS) and atopic dermatitis (AD) are the most frequent chronic and recurrent inflammatory diseases of the skin. Atopic dermatitis has a strong Th2 factor while psoriasis is a disease driven by Th17. The actual treatment, which involve the combination of topical, systemic and biological therapy, is characterized by numerous adverse effects, which reduce patient compliance, lead to the limitation of long-term use and limit the therapeutic efficacy. Therefore, there is a great need for the continuous development of novel, effective and safe coadjuvant treatments. In recent years, preclinical studies have demonstrated the role of oxidative stress in the pathogenesis of both psoriasis and atopic dermatitis and natural antioxidant compounds seem to be ideal molecules for the treatment of these diseases. For this reason, mangiferin and naringin, natural polyphenols with potent antioxidant properties were selected to be used as coadjuvant in the treatment of these diseases. However, the effectiveness of mangiferin and naringin is limited by their low solubility and low bioavailability in vivo. Thus, their incorporation into innovative and effective nanocarrier as seems to be the most suitable solution aimed at obtaining the therapeutic effect. Among the different nanocarriers, phospholipid vesicles and nanoemulsion are considered the most promising systems for the incorporation of these polyphenols and for their application on the skin. In the light of this, the aim of this work was the formulation of specific nanoemulsions and phospholipid vesicles. In particular, naringin was successfully incorporated into transfersomes, while mangiferin into nanoemulsions dispersed in hyaluronate gels and into innovative phospholipid vesicles called glycethosomes. To evaluate the possible synergistic effect, mangiferin and naringin were co-loaded into different vesicular systems: transfersomes, glycethosomes, glycerosomes, glycethohyalurosomes and glycerohyalurosomes. All the developed nanocarriers were deeply characterized by using different techniques (TEM, Cryo-TEM, Photon Correlation Spectroscopy, Rheological studies, FTIR). In vitro permeation studies were performed to evaluate the accumulation and distribution of mangiferin and naringin into and through the skin. Moreover, the protective effect of the formulations against oxidative stress damages was evaluated in mouse fibroblast cells, whereas the wound healing effect was evaluated in vivo by means of a TPA mouse model. The composition of the hydrating medium used to prepare the vesicular systems significantly affected the permeation and the capacity to restore the wound of both polyphenols. Overall results underlined that both vesicular systems and nanoemulsions can be promising systems for the treatment of psoriasis and atopic dermatitis by means of coadjuvant therapies.Chronic inflammatory skin diseases are the most common topical disorders and the fourth cause of global disability. Among all, psoriasis (PS) and atopic dermatitis (AD) are the most frequent chronic and recurrent inflammatory diseases of the skin. Atopic dermatitis has a strong Th2 factor while psoriasis is a disease driven by Th17. The actual treatment, which involve the combination of topical, systemic and biological therapy, is characterized by numerous adverse effects, which reduce patient compliance, lead to the limitation of long-term use and limit the therapeutic efficacy. Therefore, there is a great need for the continuous development of novel, effective and safe coadjuvant treatments. In recent years, preclinical studies have demonstrated the role of oxidative stress in the pathogenesis of both psoriasis and atopic dermatitis and natural antioxidant compounds seem to be ideal molecules for the treatment of these diseases. For this reason, mangiferin and naringin, natural polyphenols with potent antioxidant properties were selected to be used as coadjuvant in the treatment of these diseases. However, the effectiveness of mangiferin and naringin is limited by their low solubility and low bioavailability in vivo. Thus, their incorporation into innovative and effective nanocarrier as seems to be the most suitable solution aimed at obtaining the therapeutic effect. Among the different nanocarriers, phospholipid vesicles and nanoemulsion are considered the most promising systems for the incorporation of these polyphenols and for their application on the skin. In the light of this, the aim of this work was the formulation of specific nanoemulsions and phospholipid vesicles. In particular, naringin was successfully incorporated into transfersomes, while mangiferin into nanoemulsions dispersed in hyaluronate gels and into innovative phospholipid vesicles called glycethosomes. To evaluate the possible synergistic effect, mangiferin and naringin were co-loaded into different vesicular systems: transfersomes, glycethosomes, glycerosomes, glycethohyalurosomes and glycerohyalurosomes. All the developed nanocarriers were deeply characterized by using different techniques (TEM, Cryo-TEM, Photon Correlation Spectroscopy, Rheological studies, FTIR). In vitro permeation studies were performed to evaluate the accumulation and distribution of mangiferin and naringin into and through the skin. Moreover, the protective effect of the formulations against oxidative stress damages was evaluated in mouse fibroblast cells, whereas the wound healing effect was evaluated in vivo by means of a TPA mouse model. The composition of the hydrating medium used to prepare the vesicular systems significantly affected the permeation and the capacity to restore the wound of both polyphenols. Overall results underlined that both vesicular systems and nanoemulsions can be promising systems for the treatment of psoriasis and atopic dermatitis by means of coadjuvant therapies