Neutrophil-Mimetic oleanolic acid-loaded Liposomes targeted to alleviate oxidative stress for renal ischemia-reperfusion injury treatment
Acute kidney injury (AKI) is a prevalent clinical condition characterized by a sudden decline or loss of renal function, exacerbated by the lack of effective diagnostic and therapeutic tools. Renal ischemia-reperfusion injury serves as the primary cause of AKI, initiating a complex signaling cascade...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | International Journal of Pharmaceutics: X |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590156725000295 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Acute kidney injury (AKI) is a prevalent clinical condition characterized by a sudden decline or loss of renal function, exacerbated by the lack of effective diagnostic and therapeutic tools. Renal ischemia-reperfusion injury serves as the primary cause of AKI, initiating a complex signaling cascade that mediates renal cell necrosis, apoptosis, and inflammation. Oxidative stress plays a crucial role in the pathogenesis and progression of ischemia-reperfusion injury, thus prompting the exploration of antioxidants as potential therapeutic interventions. Oleanolic acid, derived from natural plant extracts, exhibits significant antioxidant and anti-inflammatory properties; however, its clinical application has been hindered by inherent limitations such as poor water solubility and low bioavailability. To address this issue, we developed an innovative approach involving oleanolic acid-loaded liposomes fused with neutrophil membranes, resulting in hybrid liposomes (N-OAL). This strategy aims to enhance the accumulation and retention of N-OAL at inflammatory sites associated with AKI through biomimetic chemotaxis mediated by neutrophil membranes specifically targeting damaged renal tubular epithelial cells. The optimized N-OAL presented a spherical morphology with an average particle size of 125.6 ± 4.9 nm and a surface potential of −4.8 ± 0.3 mV. In addition, N-OAL exhibited favorable sustained release, outstanding stability, and satisfactory biocompatibility. In vitro studies demonstrated that N-OAL effectively attenuated H2O2-induced intracellular reactive oxygen species generation and inflammation while exhibiting superior antioxidant and anti-apoptotic properties. Furthermore, our in vivo results confirmed the remarkable protective effect of N-OAL on oxidative-damaged renal tissue caused by AKI induction. Overall, our study provides novel insights into targeted delivery strategies for oleanolic acid therapy in acute kidney injury. |
|---|---|
| ISSN: | 2590-1567 |