Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury Treatment

Abstract

Acute kidney injury (AKI) is a common and severe problem associated with high morbidity, mortality, and healthcare costs. There are no reliable therapeutic interventions except dialysis that could improve survival, limit injury, or speed up recovery. Thus, it is essential to develop new therapies to treat AKI. Previous studies revealed that histone deacetylase inhibitor (HDACi) could attenuate renal injury and enhance kidney recovery in AKI. However, the hydrophobic nature of HDACi, such as vorinostat (SAHA), requires organic solvents to promote its dissolution, leading to inevitable detrimental effects. Herein, calcium alginate microspheres (CAM) were prepared by the microfluidic method as HDACi carriers to treat AKI by intravenous injection. First, we designed the structure of the microfluidic channel for the fabrication of the PDMS microfluidic chip in which the emulsion state of droplets was analyzed. As the flow rate increases, the continuous phase changed from laminar flow to the dripping pattern in the microfluidic device. Then, the CAM was fabricated by a W/O microfluidic emulsion template and the size of the microspheres was adjusted from 3 to 7 μm by the concentration of alginate and the flow rate of the continuous phase and dispersal phase. The higher degree of cross-linking of sodium alginate with calcium ions would lead to longer drug release time but lower swelling rates. Furthermore, we selected CAM with suitable sizes as the HDACi carrier and delivered the HDACi-loaded CAM to the AKI mice by intravenous tail injection. The in vivo results showed that the HDACi-loaded CAM could effectively reduce the renal regional inflammatory response and attenuate renal injury.