Improving Liposome Delivery with Macroporous Granular Hydrogels Synthesized through Freezing‐Facilitated Secondary Crosslinking of Macromonomers

Abstract

Abstract The integration of liposomes into hydrogels through direct soaking presents advantages such as facile formulation, enhanced drug stability, and controlled release kinetics. However, the feasibility of this approach is impeded by the difficulty of developing matching porous structures within hydrogels and achieving appropriate affinity with liposomes. To address these challenges, an alternative method is proposed for synthesizing macroporous hydrogels using thiolated hyaluronic acid and hyperbranched polyethylene glycol macromonomers in combination with a freezing‐induced secondary crosslinking process. This approach allows the locking of macropores formed by ice crystals during freezing and enables easy modification of the hydrogels with cholesterol groups to promote liposome association. Furthermore, these macroporous hydrogels can be crushed into granular hydrogels, which offer numerous benefits such as high loading capacity, injectability, self‐healing properties, and convenience in storage, dosing, and administration. Therefore, a liposome‐in‐hydrogel system can be formulated without any gelation or pre‐treatment, providing valuable insights for the further development of liposome‐based formulations for medical and cosmetic applications.