Enhanced treatment of cerebral ischemia–Reperfusion injury by intelligent nanocarriers through the regulation of neurovascular units

Lu, Hongdan; Li, Shengnan; Dai, Dongwei; Zhang, Qi; Min, Zhiyi; Yang, Chuanzhou; Sun, Shanbo; Lu, Yao; Teng, Chuanhui; Cao, Xiang; Yin, Haoyuan; Lv, Lingyan; Lv, Wei; Xin, Hongliang

doi:10.1016/j.actbio.2022.05.021

Cited by 21 publications

(10 citation statements)

References 37 publications

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“…Although the protective/therapeutic benefits of CAPE have been extensively studied [ 15 , 16 , 17 , 19 ], only a few recent studies have reported the inclusion of CAPE in a delivery system [ 22 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

A Nano-Liposomal Formulation of Caffeic Acid Phenethyl Ester Modulates Nrf2 and NF-κβ Signaling and Alleviates Experimentally Induced Acute Pancreatitis in a Rat Model

2022

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The currently available management strategies for acute pancreatitis are inadequately effective which calls for exploration of new approaches to treat this condition. Caffeic acid phenethyl ester (CAPE) is a major bioactive constituent of honeybee propolis with promising therapeutic and preventive applications. However, its pharmaceutical potential and clinical use are hindered by its poor water solubility and limited plasma stability. In this study, we aimed to prepare, characterize and evaluate a CAPE-loaded nanoliposomal formulation to improve the efficacy of CAPE for the management of acute pancreatitis. The CAPE-loaded nanoliposomes (CAPE-loaded-NL) were prepared by a thin layer evaporation technique and were optimized using three edge activators. CAPE-loaded-NL were characterized for their vesicle size (VS), zeta potential (ZP), encapsulation efficiency (EE), polydispersity index (PDI), crystalline state and morphology. The protective effect of the optimal CAPE-loaded-NL was evaluated in a rat model of acute pancreatitis induced by administering a single intraperitoneal injection of L-ornithine. Oral pretreatment with CAPE-loaded-NL significantly counteracted ornithine-induced elevation in serum activities of pancreatic digestive enzymes and pancreatic levels of malondialdehyde, nuclear factor kappa B (NF-κB) p65, tumor necrosis factor-alpha, nitrite/nitrate, cleaved caspase-3 and myeloperoxidase activity. Moreover, pretreatment with CAPE-loaded-NL significantly reinstated the ornithine-lowered glutathione reductase activity, glutathione, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 levels and ATP/ADP ratio, and potentiated the Bcl-2/Bax ratio in pancreatic tissue. CAPE-loaded-NL displayed superior antioxidant, anti-inflammatory and anti-apoptotic effects compared to free CAPE oral suspension and achieved a more potent correction of the derangements in serum amylase and pancreatic myeloperoxidase activities. The histological observations were in line with the biochemical findings. Our results suggest that CAPE-loaded-NL provide a promising interventional approach for acute pancreatitis mainly through the enhancement of the exerted antioxidant, anti-inflammatory and anti-apoptotic effects which may be mediated, at least in part, through modulation of Nrf2 and NF-κβ signaling.

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Section: Introductionmentioning

confidence: 99%

A Nano-Liposomal Formulation of Caffeic Acid Phenethyl Ester Modulates Nrf2 and NF-κβ Signaling and Alleviates Experimentally Induced Acute Pancreatitis in a Rat Model

2022

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“…These results both indicated that Lipo@GB-DHA/DID tends to accumulate in the ischemic hemisphere, meaning it could selectively target the ischemic infarct region. The phenomenon may be related to the high expression of caveolin after stroke in ischemic hemisphere, thereby increasing the endocytosis efficiency of liposomes as reported [65] . Here, BCEC cells was used as a cell model for its high expression of caveolin and pre-treated with different concentration of nystatin, which is a pharmacological blocker of caveolae-mediated endocytosis [66] .…”

Section: Resultsmentioning

confidence: 79%

Selective ischemic-hemisphere targeting Ginkgolide B liposomes with improved solubility and therapeutic efficacy for cerebral ischemia-reperfusion injury

Yang

Zhang

et al. 2023

Asian Journal of Pharmaceutical Sciences

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“…MCAO model was constructed according to our study . Mice were anesthetized with pentobarbital sodium (4% w/v) via intraperitoneal injection.…”

Section: Materials and Methodsmentioning

confidence: 99%

“…MCAO model was constructed according to our study. 47 Mice were anesthetized with pentobarbital sodium (4% w/v) via intraperitoneal injection. The external carotid artery (ECA) was separated, and the thread plug was inserted through the ECA into the internal carotid artery (ICA) until it was pushed into the middle cerebral artery (MCA).…”

Section: Materials the Polymer Dspe-tk-peg 2000 Was Obtained Frommentioning

confidence: 99%

Smart Liposomal Nanocarrier Enhanced the Treatment of Ischemic Stroke through Neutrophil Extracellular Traps and Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase-Stimulator of Interferon Genes (cGAS-STING) Pathway Inhibition of Ischemic Penumbra

Sun,

Lv,

et al. 2023

ACS Nano

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Brain inflammation is regarded as one of the leading causes that aggravates secondary brain injury and hinders the prognosis of ischemic stroke. After ischemic stroke, high quantities of peripheral neutrophils are recruited to brain lesions and release neutrophil extracellular traps (NETs), leading to the aggravation of blood−brain barrier (BBB) damage, activation of microglia, and ultimate neuronal death. Herein, a smart multifunctional delivery system has been developed to regulate immune disorders in the ischemic brain. Briefly, Cl-amidine, an inhibitor of peptidylarginine deiminase 4 (PAD4), is encapsulated into self-assembled liposomal nanocarriers (C-Lipo/CA) that are modified by reactive oxygen species (ROS)-responsive polymers and fibrin-binding peptide to achieve targeting ischemic lesions and stimuli-responsive release of a drug. In the mouse model of cerebral artery occlusion/reperfusion (MCAO), C-Lipo/CA can suppress the NETs release process (NETosis) and further inhibit the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway in an ischemic brain. In addition, MCAO mice treated with C-Lipo/CA significantly mitigated ischemic and reperfusion injury, with a reduction in the area of cerebral infarction to 12.1%, compared with the saline group of about 46.7%. These results demonstrated that C-Lipo/CA, which integrated microglia regulation, BBB protection, and neuron survival, exerts a potential therapy strategy to maximize ameliorating the mortality of ischemic stroke.

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Enhanced treatment of cerebral ischemia–Reperfusion injury by intelligent nanocarriers through the regulation of neurovascular units

Cited by 21 publications

References 37 publications

A Nano-Liposomal Formulation of Caffeic Acid Phenethyl Ester Modulates Nrf2 and NF-κβ Signaling and Alleviates Experimentally Induced Acute Pancreatitis in a Rat Model

A Nano-Liposomal Formulation of Caffeic Acid Phenethyl Ester Modulates Nrf2 and NF-κβ Signaling and Alleviates Experimentally Induced Acute Pancreatitis in a Rat Model

Selective ischemic-hemisphere targeting Ginkgolide B liposomes with improved solubility and therapeutic efficacy for cerebral ischemia-reperfusion injury

Smart Liposomal Nanocarrier Enhanced the Treatment of Ischemic Stroke through Neutrophil Extracellular Traps and Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase-Stimulator of Interferon Genes (cGAS-STING) Pathway Inhibition of Ischemic Penumbra

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