Harnessing liposomal nanocellulose hydrogel for NIR-light driven on-demand drug delivery

• Liposomal hydrogel system is developed for controlled drug delivery. • Strong electrostatic interaction makes the system stable for up to 90 days. • Near-infrared light (808 nm, 1W/cm2) was used to induce the cargo release. • Cargo release can be controlled by adjusting hydrogel thickness and dose of light. • Promising platform for on-demand and localized drug delivery. Stimuli-responsive nanoparticles have gained attention for their ability to control drug release via external signals. However, challenges like biodegradation and toxicity hinder their applications. This study introduces a system by integrating light-activated liposomes with cellulose nanofiber (CNF) hydrogel, creating a controlled release system where liposomes act as drug reservoirs, protecting drug molecules and preventing unwanted cargo leakage for on-demand localized drug delivery. Our surface interaction study between cationic liposomes and nanocellulose shows that the liposomes, while not uniformly distributed, are bound to the nanocellulose hydrogel due to strong electrostatic interactions and fiber networks, thus forming a depot-like drug reservoir system. We evaluated hydrogel thickness and light dose to optimize the cargo release. Upon activation with near-infrared light (808 nm, 1 W/cm 2 ), the photosensitizer inside the bilayer of thermosensitive liposome generates heat, which makes liposome leaky, resulting in on-demand cargo release. We observed up to 50 % release at low dose (20 J/cm 2 ) of light, which increased to 80 % after exposure to higher dose of light (80 J/cm 2 ), highlighting the sensitivity of the system. This dual-platform combines the biocompatibility of nanocellulose with tunability of light-activated liposomes, presenting promising approach for on-demand drug delivery with significant potential for personalized medicine.