Synthesis and self-assembling of hyaluronan grafted with ceramide NP for topical drug delivery

• Published in: Carbohydrate polymers 2023-12, Vol.321, p.121283-121283, Article 121283
• Main Authors: Juhaščik, Martin, Štarmanová, Kateřina, Brandejsová, Martina, Večeřová, Petra, Hermannová, Martina, Exnerová, Andrea, Vagnerová, Hana, Štrympl, Ondřej, Nešporová, Kristina, Kováčik, Andrej, Velebný, Vladimir, Huerta-Ángeles, Gloria
• Format: Article
• Language: English
• Subjects: Amphiphilic polysaccharides; Ceramides; Hyaluronan; IL-6; Self-assembling; Skin penetration
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2023.121283

In this work, amphiphilic hyaluronan was synthesized by grafting succinylated N-oleoyl-phytosphingosine via esters bonds. Succinylated N-oleoyl-phytosphingosine (sCER) was first prepared by esterification of hydroxyl moieties of the ceramide with succinic anhydride. The esterification of hyaluronan was governed by crowding effect. The oligomeric HA-sCER derivatives exhibited a strong self-aggregation as evidenced by a very low critical aggregation concentration (1.9 μg mL−1), higher pyrene binding constant (KB), and the smallest particle size (30 nm) in solution. The self-aggregation properties demonstrated to be a function of the substitution degree and molecular weight of HA. The prepared derivatives were non-cytotoxic towards cell lines NIH-3T3. Nanoparticles prepared using oligomeric HA-sCER derivatives improved the penetration of Nile red dye through the stratum corneum due to their smaller size (≤50 nm). The fluorescence intensity localized at the stratum corneum was higher for oligomeric HA-sCER. A significant inhibition of the pro-inflammatory cytokine interleukin-6 production was observed in vitro in macrophages differentiated from THP-1 cells. These findings showed that HA-sCER constituted a promising active ingredient for cosmetics use. [Display omitted]