Wydział Chemii

Elisabetta Esposito

Valentyn Dzyhovskyi

Federico Santamaria

Lorenza Marvelli

Paola Boldrini

Paolo Mariani

Alessia Pepe

Maria Grazia Ortore

Mascia Benedusi

Giuseppe Valacchi

Luca Ferraro

2025

Journal of Pharmacy and Pharmaceutical Sciences

28

15553/1-15553/15

10.3389/jpps.2025.15553

Naukowa

Angielski

Artykuł

Objective: 

Despite the antioxidant, anti-inflammatory, and anti-cellular-aging activities of urolithin A (UroA), a naturally occurring postbiotic, its high lipophilicity hampers its pharmaceutical application. To overcome this limitation improving its stability and bioavailability, submicron emulsions (S-EMs) were designed.

Methods: 

Nineteen formulations (S-EM 1/S-EM 19) were prepared by two different methodologies. S-EMs were characterized evaluating macroscopical appearance and size distribution by photon correlation spectroscopy (PCS). One selected S-EM was loaded with UroA and characterized by PCS, transmission electron microscopy (TEM), small angle x-ray scattering (SAXS) and Fourier-transform infrared spectroscopy (FT-IR). Z potential, pH and syringeability were evaluated. UroA entrapment was studied efficiency by ultrafiltration and HPLC, while in vitro release by dialysis. Cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) viability test on primary dermal human fibroblasts. The anti-inflammatory activity of S-EM-UroA was evaluated at 3, 6, and 24 h post-injection using the carrageenan-induced paw edema model in male C57BL/6 mice, and compared with UroA suspension and unloaded S-EM.

Results: 

The preformulative study enabled to select method and composition for S-EM preparation. S-EM 18 was selected for UroA loading (SEM-UroA), due to mean diameter, zeta potential, pH and syringeability suitable for intraperitoneal administration. The loading of UroA (0.2 mg/mL) did not influence S-EM physicochemical features, while maintaining technological properties for 3 months. In vitro drug release showed a biphasic profile, 2.35-fold faster in the case of SEM-UroA compared to the drug suspension. In vitro studies revealed absence of cytotoxicity at concentrations up to 5 µM. In vivo studies, conducted as a first step in assessing the potential of S-EM-UroA, demonstrated a dose-dependent anti-inflammatory effect. Specifically, S-EM-UroA at 2 mg/kg reduced paw edema at 24 h (p < 00.5; One-Way ANOVA followed by Tukey’s test), and at 4 mg/kg significantly reduced edema at all time points (p < 0.01), whereas the UroA suspension or S-EM had no effect on carrageenan-induced paw edema at any time point.

Conclusion: 

These findings underscore the potential of UroA loaded S-EM as an effective delivery system, demonstrating its superiority over simple UroA suspensions in enhancing the systemic anti-inflammatory effects of the postbiotic.

urolithin-A, ellagic acid, submicron emulsion, dialysis, carrageenan-induced paw edema model

CC-BY

http://dx.doi.org/10.3389/jpps.2025.15553

http://www.frontiersin.org/plant_science/about