Anthocyanins-quercetin copigmentation enhances liposomal encapsulation: Mechanisms, bilayer interactions, and sustained release performance

Conventional liposome preparation techniques often show poor encapsulation efficiency (EE) for hydrophilic compounds. In this study, copigmentation was employed as a hydrophobic modification strategy to improve the liposomal delivery of anthocyanins (ACNs). ACNs formed stable copigmentation complexes with quercetin (QTI), primarily through π–π stacking and hydrophobic interactions. These interactions enhanced the hydrophobicity of ACNs and promoted their redistribution from the aqueous phase toward the bilayer interfacial region. Liposomes prepared by the polyol dilution method encapsulated ACNs@QTI complexes more efficiently than free ACNs, achieving an EE of 81.5 ± 0.6% and a particle size of 166.4 ± 7.9 nm. FTIR, DSC, and fluorescence analyses confirmed stronger interactions between ACNs@QTI complexes and phospholipid membranes, while in-vitro release experiments demonstrated its superior sustained-release performance. These findings highlight copigmentation as a practical non-covalent strategy to enhance liposomal encapsulation of hydrophilic bioactives, offering a basis for enhancing the stability and delivery of ACNs and other water-soluble compounds in food and pharmaceutical applications.