A Closed-Loop Autologous Erythrocyte-Mediated Delivery Platform for Diabetic Nephropathy Therapy

Abstract

Failure to control blood glucose level (BGL) may aggravate oxidative stress and contribute to the development of diabetic nephropathy (DN). Using erythrocytes (ERs) as the carriers, a smart self-regulatory insulin (INS) release system was constructed to release INS according to changes in BGLs to improve patients’ compliance and health. To overcome the limited sources of ERs and decrease the risk of transmitting infections, we developed an in vitro, closed-loop autologous ER-mediated delivery (CAER) platform, based on a commercial hemodialysis instrument modified with a glucose-responsive ER-based INS delivery system (GOx-INS@ER). After the blood was drained via a jugular vein cannula, some of the blood was pumped into the CAER platform. The INS was packed inside the autologous ERs in the INS reactor, and then their surface was modified with glucose oxidase (GOx), which acts as a glucose-activated switch. In vivo, the CAER platform showed that the BGL responsively controlled INS release in order to control hyperglycemia and maintain the BGL in the normal range for up to 3 days; plus, there was good glycemic control without the added burden of hemodialysis in DN rabbits. These results demonstrate that this closed-loop extracorporeal hemodialysis platform provides a practical approach for improving diabetes management in DN patients.

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“…Feng et al proposed a closed-loop autologous ER-mediated delivery (CAER) platform to circumvent the limited supply of erythrocytes and decrease the infection transmission risk (Figure 4). [180] This platform is based on a commercial hemodialysis instrument modified with a glucose-responsive ER-based insulin delivery system (GOx-INS@ER). The CAER platform can control the BGL well and complete hemodialysis in an in vivo rabbit model with diabetic nephropathy.…”

“…Reproduced under the terms of Creative Commons CC BY license. [ 180 ] The Authors, published by MDPI.…”

“…B) Images of the actual products, including the jugular vein cannula, INS reactor, GOx reactor, and hemodialysis equipment. Reproduced under the terms of Creative Commons CC BY license [180]. The Authors, published by MDPI.…”