Enzyme-functionalized hydrogel film for extracorporeal uric acid reduction

Abstract

Enzyme replacement therapy for hyperuricemia treatment has been proven effective for critical state hyperuricemia patients. Still, direct administration of recombinant uricase can induce several fatal side effects. To circumvent this drawback, hydrogel protein carriers can be used in platforms for extracorporeal treatment such as microscale-based devices. In this work, calcium alginate and poly-(vinyl alcohol) hydrogel films were studied for their urate oxidase immobilization and uric acid reduction, which could be implemented in microscale-based extracorporeal devices. A mathematical model was developed in conjunction with uric acid reduction experiments to evaluate the influence of mass transfer and reaction parameters in the Michaelis-Menten kinetic expression. Alginate hydrogels prepared with crosslinker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-(hydroxysuccinimide) offered superior diffusivity of uric acid in the gel matrix at the maximum value of $D_{g,\mathrm{UA}}\approx$ 1.98 × 10^-11 m² /s compared with alginate prepared solely from ionic crosslinking with $D_{g,\mathrm{UA}}\approx$ 5.31 × 10^-12 m² /s at the same alginate concentration. The maximum value of ν_max was experimentally determined at 7.78 × 10^-5 mol/(m³ s). A 3% sodium alginate hydrogel with crosslinkers yielded the highest reduction of uric acid at 92.70%. The mathematical model demonstrated an excellent prediction of uric acid conversion suggesting potential use of the model for formulation and maximizing the therapeutic performance of functionalized hydrogels.

Keywords: hydrogel films; hyperuricemia; mathematical modeling; numerical simulation; uric acid.