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Layered Double Hydroxide-Loaded Dl-3-n-Butylphthalide Alleviates Renal Ischemia-Reperfusion Injury by Regulating the
1Department of Anesthesiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, People's Republic of China.
International Journal of Nanomedicine
|April 22, 2026
Summary
This study developed a novel nano-drug delivery system using layered double hydroxide (LDH) to improve the therapeutic efficacy of Dl-3-n-butylphthalide (NBP) for renal ischemia-reperfusion injury. The LDHs-NBP nanocomplexes demonstrated significant protective effects by activating the PI3K-AKT-Nrf2 pathway.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Pharmacology
Background:
- Dl-3-n-butylphthalide (NBP) exhibits therapeutic potential but is limited by poor water solubility and low bioavailability.
- Renal ischemia-reperfusion (I/R) injury is a critical condition with significant clinical challenges.
- Developing effective drug delivery systems is crucial for enhancing NBP's therapeutic outcomes in renal injury.
Purpose of the Study:
- To address the limitations of NBP's clinical application by developing a novel nano-drug delivery system.
- To enhance the stability and efficacy of NBP using layered double hydroxide (LDH) nanoparticles.
- To investigate the therapeutic potential and underlying mechanism of NBP-loaded LDH (LDHs-NBP) in renal I/R injury.
Main Methods:
- Construction of LDHs-NBP nanocomplexes via NBP loading onto LDH.
- Systematic evaluation of LDHs-NBP effects on renal function, tissue pathology, apoptosis, oxidative stress, and mitochondrial function in rat renal I/R models and HK-2 cell hypoxia/reoxygenation models.
- Analysis of the PI3K-AKT-Nrf2 signaling pathway activation using immunohistochemistry and Western Blot.
Main Results:
- LDHs-NBP nanocomplexes achieved a drug loading capacity of 24.26%.
- LDHs-NBP significantly improved renal function, reduced serum creatinine (SCr) and blood urea nitrogen (BUN), and mitigated renal tissue damage and inflammation compared to pure NBP.
- LDHs-NBP demonstrated potent antioxidant effects, inhibited apoptosis and ROS production in HK-2 cells, alleviated mitochondrial dysfunction, and activated the PI3K-AKT-Nrf2 signaling pathway.
Conclusions:
- Successfully constructed NBP nano-complexes based on LDH (LDHs-NBP) with enhanced therapeutic advantages for renal I/R injury.
- The protective mechanism of LDHs-NBP in renal I/R injury is associated with the activation of the PI3K-AKT-Nrf2 pathway.
- LDHs-NBP shows promising translational prospects and clinical value for treating renal I/R injury.
