From sustainable fermentation to Smart Nanocarriers: Sophorolipid -Phospholipid Hybrid vesicles with Antibacterial and Antiproliferative activity

Sophorolipids (SLs) are microbial glycolipids with amphiphilic properties that have attracted attention as sustainable bioactive molecules with potential applications in antimicrobial and anticancer therapies. In this study, we evaluated how the degree of purification (crude, partially purified and purified) and the structural type of SLs (diacetylated lactonic) influence their physicochemical characteristics and biological activities, and we further investigated their performance when formulated into hybrid phospholipid-based vesicles. Specifically, the enrichment in lactonic C18:1 congeners (>90% in the purified SLs) through consecutive purifications steps led to lower critical micelle concentration (CMC) values and enhanced the stability of the resulting formulations in terms of Z-average and polydispersity index (PDI). Purified SLs showed strong antimicrobial activity against Gram-positive bacteria with minimum inhibitory concentrations (MIC) comparable to gentamicin and lower activity against Gram-negative and Candida spp. In addition, purified SLs demonstrated marked antiproliferative effects on two selected breast cancer cell lines (SK-BR-3 and DA-MB-231), with IC 50 values in agreement with those reported in the literature. The formation of hybrid vesicles composed of purified SLs and DMPC retained the antimicrobial and cytotoxic activity with the respect to free SLs, supporting the potential application of these delivery systems. Overall, the results highlighted the critical role of purity and structural type in determining the functional properties of SLs together with the exploitation of vesicular formulations in enhancing their applicability. These findings provide a foundation for the rational development of SLs-based therapeutics and encourage further in vivo evaluation of their efficacy and safety. • Sustainable solid-state fermentation yields bioactive sophorolipids • Purity grade strongly influences sophorolipid self-assembly and bioactivity • Purified sophorolipids (lactonic C18:1) form stable hybrid vesicles with phospholipids • Hybrid vesicles show potent antimicrobial and anti-breast cancer effects • Sophorolipid–phosholipid systems are promising multifunctional nanocarriers