Design and Optimization of Pullulan-Isononanoate Films with Bioactive-Loaded Liposomes for Potential Biomedical Use

This study reports the synthesis and detailed characterization of pullulan-isononanoate (Pull-Iso), as well as the preparation and characterization of Pull-Iso films incorporating liposomes loaded with silibinin (SB) and smoke tree (Cotinus coggygria) extract (STExt), to explore the physicochemical and functional properties of pullulan-based biomaterials for potential biomedical applications. Pullulan was successfully esterified with isononanoic acid chloride, as confirmed by ¹H and ¹³C NMR (Nuclear Magnetic Resonance) and Fourier Transform Infrared (FTIR) spectroscopy. Modification significantly reduced the glass transition temperature (Tg), indicating enhanced chain mobility due to the introduction of bulky side chains. Prepared liposomes, embedding SB and extracted smoke tree compounds, exhibited particle sizes ~2000 nm with moderate polydispersity (~0.340) and zeta potential values around -20 mV, demonstrating lower colloidal stability over 60 days, thereby justifying their encapsulation within films. Optical microscopy revealed uniform liposome dispersion in Pull-Iso film with 0.5 g of liposomes, while higher liposome loading (0.75 g of liposomes) induced aggregation and microstructural irregularities. Mechanical analysis showed a reduction in tensile strength and strain at higher liposome content. The incorporation of liposomes encapsulating STExt and SB significantly enhanced the antioxidant activity of Pull-Iso-based films in a concentration-dependent manner, as demonstrated by DPPH and ABTS radical scavenging assays. These preliminary findings suggest that pullulan esterification and controlled liposome incorporation may enable the development of flexible, bioactive-loaded films, which could represent a promising platform for advanced wound dressing applications, warranting further investigation.