Uricase and Horseradish Peroxidase Hybrid CaHPO₄ Nanoflower Integrated with Transcutaneous Patches for Treatment of Hyperuricemia.

Abstract

Currently, there are approximately 170 million hyperuricemia patients in China. Conventional drug therapy has limited clinical benefits and may induce serious side effects. Enzyme replacement therapy has attracted much attention owing to its advantages of strong specificity, small dosage, and remarkable curative effect. Uricase is an efficient oxidase, which can oxidize uric acid to allantoin and hydrogen peroxide, to reduce the uric acid level. In this study, we used a mild biomimetic method to prepare a novel uricase and horseradish peroxidase (HRP) loaded CaHPO₄ nanoflower (uricase&HRP-CaHPO₄ nanoflower). The nanoflower was then integrated with a hyaluronic acid dissolvable microneedle system (uricase&HRP-CaHPO₄ @HA MN) to achieve transdermal drug delivery for the treatment of hyperuricemia, which has high patient compliance. In this system, the stability and catalytic activity of uricase could be improved by the CaHPO₄ nanoflower, and HRP could decompose the hydrogen peroxide to accelerate the reaction of uricase. An in vivo study demonstrated that the uricase&HRP-CaHPO₄ @HA MN could effectively reduce the uric acid level of blood as intravenous injection without side effects. Thus, this uricase&HRP-CaHPO₄ @HA MN can facilitate transcutaneous hyperuricemia treatment and provide a new alternative for the exploration of clinical treatment of hyperuricemia.