Liposomal Encapsulation of Hardy Kiwi (Actinidia arguta) Bioactives: Optimization, Characterization and Biological Screening in Physiological Barrier Models

Phenolic compounds from fruits, such as Actinidia arguta (hardy kiwi), are associated with numerous health benefits. However, their application is often limited by poor stability, low bioaccessibility, and restricted cellular uptake. To overcome these limitations, liposomal nanodelivery systems have emerged as an effective strategy to protect bioactive compounds and enhance their delivery across biological barriers. This study aims to develop and optimize phospholipid-based liposomes encapsulating a phenolic-rich extract from hardy kiwi and to evaluate their physicochemical characteristics and biological response in physiological barrier models. Liposomes were prepared by sonication and optimized using a response surface methodology (RSM) coupled with a central composite design (CCD). The optimized formulation, containing 167.86 mg/mL lecithin, 42.45 mg/mL extract, and 28.94% sonication amplitude, yielded a mean vesicle size of 107.2 nm, low polydispersity (0.173), high negative zeta potential (−46.9 mV), and 50.73% encapsulation efficiency, indicating good colloidal stability. The phenolic profile of the extract and its successful incorporation into the liposomal matrix were confirmed by UPLC-QTOF-ESI-MS analysis. Furthermore, DSC, FTIR, and TEM characterization demonstrated the structural integrity and nanoscale organization of the developed liposomal systems. The biological response promoted by the liposomal system was evaluated by MTT assays using cell models representative of intestinal, endothelial, skin, and cancer barriers, revealing that liposomal encapsulation influenced cellular responses and interactions depending on the biological model evaluated. Overall, the optimized liposomal system showed suitable physicochemical properties and effective incorporation of A. arguta phenolic compounds, highlighting its potential as a nanodelivery platform for the targeted application of hardy kiwi bioactives across different physiological barriers.