An injectable polyelectrolyte chitosan-based lipogel containing silver nanoprisms as a multifunctional platform for drug delivery

Injectable chitosan-based gels that combine tunable mechanical properties, stimuli-responsiveness and sustained release of hydrophilic drugs remain challenging to develop without chemical modification and/or cross-linking, which can affect the gel's biological properties. To overcome this, herein, a self-assembled polyelectrolyte chitosan-based gel blended with silver nanoprism (AgNPs)-loaded liposomes is presented. The gel was developed by pH-triggered self-assembly, avoiding the potential toxicity and complexity of chemical cross-linkers, enabling fast gelation, injectability, and tunable mechanical properties. Photostable AgNPs (~60 nm) with a near-infrared radiation (NIR) conversion efficiency of 35.7% were obtained through a reduction approach employing glucose. The AgNPs-loaded liposomes enabled the development of chitosan lipogels with a large storage modulus (~2 kPa) at low polymer concentration (1 wt%), thermal responsiveness, and the prolonged release of a model drug, 5-fluorouracil. The lipogels were found to be cytocompatible and outperformed the hydrogel and free drug against triple-negative breast cancer (TNBC) cells. Hereby, the self-assembled chitosan-based lipogels are highlighted as a promising platform for localized drug delivery applications.