초록 |
Biological drugs are tailored components offering the advantages that are considered safe for treating diseases. Nevertheless, the effectiveness of biological drugs is limited by their short biological half-life and poor stability in vivo. Herein, we engineered a novel delivery platform based on hybrid injectable hydrogels, in which pH/temperature-responsive biodegradable copolymers, were site-specifically coupled to the sulfhydryl group of human serum albumin, which effectively enhances the stability and circulation half-life of the biological drug, recombinant uricase enzyme (Uox). The albumin ligand conjugated to the Uox allowed specific-binding of the enzyme within the protein shell, and synthetic polymers effectively shield the protein-enzyme complex. Subcutaneous administration of Uox-loaded hybrid hydrogel improved the pharmacokinetics by prolonging its circulation half-life. As a result, the hybrid hydrogel normalized the serum uric acid level in hyperuricemia mice. The characteristic of the hybrid hydrogel networks applicable to a variety of drugs by simple mixing that unlock the possibility of adapting drugs to therapeutic applications. |