Structure-activity relationship of adipate-bridged β-sitosterol glycosyl derivatives as novel cholesterol alternatives for liposome stabilization.

Liposomes stabilized by adipate-bridged β-sitosterol glycosyl derivatives (hereafter, β-sitosterol glycosyl adipates) were characterized to elaborate their structure-activity relationship (SAR) as effective cholesterol alternatives. Compared with liposomes stabilized by cholesterol or β-sitosterol, those stabilized by β-sitosterol glycosyl adipates exhibited improved bilayer structural properties. Among all formulations, liposomes stabilized by β-sitosterol sucrose adipate possessed the most compact lipid packing and the smallest particle size (<80 nm). After curcumin (Cur) loading, the optimized liposomes reached an encapsulation efficiency of 78.67% ± 2.13%, maintained an apparent Cur retention rate above 97% over 28-day storage at 25 °C, and achieved in vitro bioaccessibility exceeding 44%. SAR analysis revealed that hydrogen-bonding interactions and glycosyl steric hindrance worked synergistically to regulate the physicochemical and functional properties of the liposomes. This study facilitates the development of amphiphilic phytosterol derivatives and supports the design of efficient cholesterol-free liposomal carrier systems for food applications.