Albumin hydrogels for repeated capture of drugs from the bloodstream and release into the tumor

Abstract

Despite the efficacy of hydrogels for consistently delivering drugs to targeted areas (primarily tumors), these systems face challenges such as initial burst release, non-refillable drugs, and a lack of dosage control. To address these issues, a novel strategy has been developed to capture and release drugs from the bloodstream, thereby overcoming the limitations of traditional hydrogels. In this study, an innovative albumin hydrogel system was developed through a bioorthogonal reaction using azide-modified albumin and 4-arm PEG-DBCO. This system can repeatedly capture and release drugs over prolonged periods. Inspired by albumin-drug binding in vivo, this hydrogel can be injected intratumorally and acts as a reservoir for capturing drugs circulating in the bloodstream. Drugs captured in hydrogels are released slowly and effectively delivered to tumors through a “capture and release process.” Both the in vitro and in vivo results indicated that the hydrogel effectively captured and released drugs, such as indocyanine green and doxorubicin, over repeated cycles without compromising the activity of the drugs. Moreover, implanting the hydrogel at surgical sites successfully inhibited tumor recurrence through its drug capture-release capability. These findings establish the albumin hydrogel system as a promising capture-release platform that leverages drug-binding affinity to effectively deliver drugs to tumors, offering potential advancements in cancer treatment and post-surgery recurrence prevention.