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...

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Main Authors: Qiaojing Chen, Daping Xiao, Yi Wang, Zheng Zhang, Xinlu Lin, Qing Ji, Yingmin Han, Lingan Yu, Jinglin Xu
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:International Journal of Pharmaceutics: X
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590156725000295
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author Qiaojing Chen
Daping Xiao
Yi Wang
Zheng Zhang
Xinlu Lin
Qing Ji
Yingmin Han
Lingan Yu
Jinglin Xu
author_facet Qiaojing Chen
Daping Xiao
Yi Wang
Zheng Zhang
Xinlu Lin
Qing Ji
Yingmin Han
Lingan Yu
Jinglin Xu
author_sort Qiaojing Chen
collection DOAJ
description 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.
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spelling doaj-art-43331d60b5684346843a6bddf4ac7c092025-08-20T02:37:06ZengElsevierInternational Journal of Pharmaceutics: X2590-15672025-06-01910034410.1016/j.ijpx.2025.100344Neutrophil-Mimetic oleanolic acid-loaded Liposomes targeted to alleviate oxidative stress for renal ischemia-reperfusion injury treatmentQiaojing Chen0Daping Xiao1Yi Wang2Zheng Zhang3Xinlu Lin4Qing Ji5Yingmin Han6Lingan Yu7Jinglin Xu8Department of Nephrology, Huangyan Hospital, Wenzhou Medical University, Taizhou, ChinaDepartment of Nephrology, Huangyan Hospital, Wenzhou Medical University, Taizhou, ChinaDepartment of Pharmacy, Taizhou Women and Children's Hospital of Wenzhou Medical University, Taizhou, ChinaDepartment of Nursing, Taizhou Women and Children's Hospital of Wenzhou Medical University, Taizhou, ChinaDepartment of Pharmacy, Huangyan Hospital, Wenzhou Medical University, Taizhou, ChinaDepartment of Nephrology, Huangyan Hospital, Wenzhou Medical University, Taizhou, ChinaDepartment of Nephrology, Huangyan Hospital, Wenzhou Medical University, Taizhou, ChinaDepartment of Nephrology, Huangyan Hospital, Wenzhou Medical University, Taizhou, China; Corresponding authors.Department of Nephrology, Huangyan Hospital, Wenzhou Medical University, Taizhou, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2590156725000295Ischemia/reperfusion injuryOxidative stressNeutrophil-mimeticLiposomeOleanolic acid
spellingShingle Qiaojing Chen
Daping Xiao
Yi Wang
Zheng Zhang
Xinlu Lin
Qing Ji
Yingmin Han
Lingan Yu
Jinglin Xu
Neutrophil-Mimetic oleanolic acid-loaded Liposomes targeted to alleviate oxidative stress for renal ischemia-reperfusion injury treatment
International Journal of Pharmaceutics: X
Ischemia/reperfusion injury
Oxidative stress
Neutrophil-mimetic
Liposome
Oleanolic acid
title Neutrophil-Mimetic oleanolic acid-loaded Liposomes targeted to alleviate oxidative stress for renal ischemia-reperfusion injury treatment
title_full Neutrophil-Mimetic oleanolic acid-loaded Liposomes targeted to alleviate oxidative stress for renal ischemia-reperfusion injury treatment
title_fullStr Neutrophil-Mimetic oleanolic acid-loaded Liposomes targeted to alleviate oxidative stress for renal ischemia-reperfusion injury treatment
title_full_unstemmed Neutrophil-Mimetic oleanolic acid-loaded Liposomes targeted to alleviate oxidative stress for renal ischemia-reperfusion injury treatment
title_short Neutrophil-Mimetic oleanolic acid-loaded Liposomes targeted to alleviate oxidative stress for renal ischemia-reperfusion injury treatment
title_sort neutrophil mimetic oleanolic acid loaded liposomes targeted to alleviate oxidative stress for renal ischemia reperfusion injury treatment
topic Ischemia/reperfusion injury
Oxidative stress
Neutrophil-mimetic
Liposome
Oleanolic acid
url http://www.sciencedirect.com/science/article/pii/S2590156725000295
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