The Hybrid Hydrogel for Sustained Release and Extended Half-life: Albumin Affibody-Conjugated Injectable Gel with Albumin-Conjugated Urate Oxidase for the Treatment of Hyperuricemia
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초록
내용
The short half-life of therapeutic proteins is usually a bottleneck for their clinical application. Injectable hydrogels have been used as depots for the controlled release of therapeutic proteins. However, the native interactions between therapeutic protein and hydrogel are often not sufficient to achieve extended release of the therapeutic protein. Herein, we investigated whether a pair of HSA and its very strong ligand, albumin-binding peptide (ABP), can be used to achieve substantially extended release of therapeutic protein from injectable hydrogel. HSA was conjugated to a therapeutic protein. The ABP was conjugated to pH- and temperature-sensitive poly(ethylene glycol)-poly(β-amino ester urethane) (PEG-PAEU) copolymer. As a result, the serum activity half-life of the Uox-HSA conjugate loaded in the ABP-modified PEG-PAEU hydrogels was 96 h, which was much longer than those of free native Uox, free Uox-HSA, and Uox-HSA conjugate loaded in the unmodified PEG-PAEU hydrogels.