Development of liposomal and polymeric nanocarriers for luteolin delivery: A senolytic-oriented approach

Luteolin is a naturally occurring flavonoid with growing interest for its senolytic properties. However, its poor water solubility and low bioavailability limit clinical application. This study aimed to develop and compare two types of nanocarriers, liposomes and polymeric nanoparticles, for the efficient delivery of luteolin in senolytic therapies. Liposomes with luteolin were prepared using the lipid film hydration method, followed by sonication and extrusion. Polymeric nanoparticles were developed via the nanoprecipitation method using pullulan acetate, a hydrophobic derivative obtained by chemical functionalization of pullulan. Pullulan was biosynthesized over 72 hours using the microorganism Aureobasidium pullulans ICCF 36 (from CMII – INCDCF-ICCF). The formulation used a polymer-to-luteolin ratio of 10:1 (g/g) and Pluronic F127 as a stabilizer. Nanoprecipitation was carried out under controlled conditions: stirring at 700 rpm and dropwise addition at 0.5 mL/min. Luteolin was successfully encapsulated in both delivery systems. Liposomes showed an encapsulation efficiency of 85.07 ± 0.09% and nanoscale diameter. Polymeric nanoparticles demonstrated an encapsulation efficiency of 74.87 ± 0.05% ,nanometric size and a formulation yield of 73.29 ± 0.09%. Both liposomal and polymeric nanoparticle systems effectively encapsulated luteolin, with high efficiency and yield. The formulations present promising potential for use in senolytic therapies, targeting age-related cellular dysfunction. Further studies will assess their release kinetics, biological activity, and senolytic effects in vitro and in vivo.

Acknowledgements: This work was suported through the “Nucleu” Program, Contract no. 1N/2023, Project code PN 23-28 carried out with the support of MCID, project no. PN 23-28 03 01.