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

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...

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Main Authors: Jia Man, Xiaojie Wang, Jianyong Li, Xiaoyang Cui, Zesheng Hua, Jianfeng Li, Zebing Mao, Shanguo Zhang
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Micromachines
Subjects:
Online Access:https://www.mdpi.com/2072-666X/13/4/538
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author Jia Man
Xiaojie Wang
Jianyong Li
Xiaoyang Cui
Zesheng Hua
Jianfeng Li
Zebing Mao
Shanguo Zhang
author_facet Jia Man
Xiaojie Wang
Jianyong Li
Xiaoyang Cui
Zesheng Hua
Jianfeng Li
Zebing Mao
Shanguo Zhang
author_sort Jia Man
collection DOAJ
description 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.
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spelling doaj.art-183b32d67ba344de99c2afcd96b912b62023-11-30T21:33:48ZengMDPI AGMicromachines2072-666X2022-03-0113453810.3390/mi13040538Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury TreatmentJia Man0Xiaojie Wang1Jianyong Li2Xiaoyang Cui3Zesheng Hua4Jianfeng Li5Zebing Mao6Shanguo Zhang7Key Laboratory of High Efficiency and Clean Mechanical Manufacture of MOE, School of Mechanical Engineering, Shandong University, Jinan 250061, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan 250012, ChinaKey Laboratory of High Efficiency and Clean Mechanical Manufacture of MOE, School of Mechanical Engineering, Shandong University, Jinan 250061, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan 250012, ChinaKey Laboratory of High Efficiency and Clean Mechanical Manufacture of MOE, School of Mechanical Engineering, Shandong University, Jinan 250061, ChinaKey Laboratory of High Efficiency and Clean Mechanical Manufacture of MOE, School of Mechanical Engineering, Shandong University, Jinan 250061, ChinaSmart Materials Lab, Department of Engineering Science and Mechanics, Shibaura Institute of Technology, 3-7-5 Toyosu, Koto-ku, Tokyo 135-8548, JapanKey Laboratory of High Efficiency and Clean Mechanical Manufacture of MOE, School of Mechanical Engineering, Shandong University, Jinan 250061, ChinaAcute 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.https://www.mdpi.com/2072-666X/13/4/538drug deliveryalginate microspheresmicrofluidicacute kidney injury treatmentintravenous injection therapy
spellingShingle Jia Man
Xiaojie Wang
Jianyong Li
Xiaoyang Cui
Zesheng Hua
Jianfeng Li
Zebing Mao
Shanguo Zhang
Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury Treatment
Micromachines
drug delivery
alginate microspheres
microfluidic
acute kidney injury treatment
intravenous injection therapy
title Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury Treatment
title_full Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury Treatment
title_fullStr Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury Treatment
title_full_unstemmed Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury Treatment
title_short Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury Treatment
title_sort intravenous calcium alginate microspheres as drug delivery vehicles in acute kidney injury treatment
topic drug delivery
alginate microspheres
microfluidic
acute kidney injury treatment
intravenous injection therapy
url https://www.mdpi.com/2072-666X/13/4/538
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