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A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
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Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury Treatment
Jia Man1,2, Xiaojie Wang3, Jianyong Li1,2
1Key Laboratory of High Efficiency and Clean Mechanical Manufacture of MOE, School of Mechanical Engineering, Shandong University, Jinan 250061, China.
Micromachines
|April 23, 2022
Summary
New calcium alginate microspheres effectively deliver histone deacetylase inhibitors to treat acute kidney injury (AKI). This innovative carrier system reduces inflammation and renal injury in mice, offering a promising therapeutic strategy for AKI.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Nephrology
Background:
- Acute kidney injury (AKI) presents significant morbidity, mortality, and healthcare burdens.
- Current AKI treatments are limited, with dialysis being the primary intervention.
- Histone deacetylase inhibitors (HDACi) show potential for AKI treatment but face delivery challenges due to hydrophobicity.
Purpose of the Study:
- To develop a novel carrier system for HDACi to treat AKI.
- To utilize microfluidics for fabricating calcium alginate microspheres (CAM) as HDACi carriers.
- To evaluate the efficacy of HDACi-loaded CAM in an in vivo AKI model.
Main Methods:
- Fabrication of a microfluidic chip for CAM synthesis.
- Optimization of CAM size (3-7 μm) by controlling alginate concentration and flow rates.
- Intravenous administration of HDACi-loaded CAM in a mouse model of AKI.
Main Results:
- Successfully fabricated CAM with tunable sizes using a W/O microfluidic emulsion template.
- Demonstrated that higher cross-linking of CAM leads to longer drug release but reduced swelling.
- In vivo studies showed HDACi-loaded CAM significantly reduced renal inflammation and attenuated kidney injury in AKI mice.
Conclusions:
- CAM prepared via microfluidics serve as effective carriers for hydrophobic HDACi.
- This delivery system overcomes the limitations of organic solvents for HDACi administration.
- HDACi-loaded CAM represent a promising therapeutic approach for mitigating renal injury in AKI.
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