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 (<i>Cotinus coggygria</i>) 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 (<i>Tg</i>), 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.