In situ facile-forming PEG cross-linked albumin hydrogels loaded with an apoptotic TRAIL protein

Abstract The key to making a practicable hydrogel for pharmaceutical or medical purposes is to endow it with relevant properties, i.e., facile fabrication, gelation time-controllability, and in situ injectability given a firm basis for safety/biocompatibility. Here, the authors describe an in situ gelling, injectable, albumin-cross-linked polyethylene glycol (PEG) hydrogel that was produced using a thiol-maleimide reaction. This hydrogel consists of two biocompatible components, namely, thiolated human serum albumin and 4-arm PEG_20k-maleimide, and can be easily fabricated and gelled in situ within 60 s by simply mixing its two components. In addition, the gelation time of this system is controllable in the range 15 s to 5 min. This hydrogel hardly interacted with an apoptotic TRAIL protein, ensuring suitable release profiles that maximize therapeutic efficacy. Specifically, tumors (volume: 278.8 mm³) in Mia Paca-2 cell-xenografted BALB/c nu/nu mice treated with the TRAIL-loaded HSA-PEG hydrogel were markedly smaller than mice treated with the hydrogel prepared via an amine-N-hydroxysuccinimide reaction or non-treated mice (1275.5 mm³ and 1816.5 mm³, respectively). We believe that this hydrogel would be a new prototype of locally injectable sustained-release type anti-cancer agents, and furthermore offers practical convenience for a doctor and universal applicability for a variety of therapeutic proteins.