JOURNAL OF NANOBIOTECHNOLOGY
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2025
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IF 12.6
Zhe Zhang,Guangyu Jia,Qi Wang,Yamei Yu,Xiaolong Tang,Heqing Zheng,Xinyu Yang,Yao Xiao,Yangrui Ou,Jingjing Jiang,Hua Guo,Ye Wang,Shiyong Li
Intranasal drug delivery via nanocarriers has long been a research focus for enhancing drug concentration in the brain. However, the strategy of exploiting blood–brain barrier (BBB) alterations in atherosclerotic mouse models to enhance nanoparticle-mediated delivery of bromocriptine to the hypothalamus for the treatment of prolactinomas with hyperprolactinemia has not yet been reported. This study reveals that in patients with prolactinomas complicated by arteriosclerosis, bromocriptine therapy more effectively attenuates postoperative elevations in prolactin levels. In a mouse model, liposome-encapsulated bromocriptine efficiently traversed the nasal mucosa and entered the intracranial space. Compared with normal mice, bromocriptine-loaded liposomes delivered higher bromocriptine concentrations to the hypothalamus. Single-cell RNA sequencing revealed a significant upregulation of organic anion-transporting polypeptide 1a4 (Oatp1a4) expression in the brain endothelial cells of atherosclerotic mice. Importantly, bromocriptine-loaded liposomes more effectively reduced prolactin levels in a mouse model of prolactinoma with concurrent atherosclerosis. This study provides a theoretical foundation for the precision treatment of prolactinomas in arteriosclerosis.
研究领域:
药理学
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神经科学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
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IF 11.467
Da-Yuan Wang,Guang Yang,Xiao-Xiao Zhang,Henny C. van der Mei,Yijin Ren,Henk J. Busscher,Linqi Shi
Exposure of infectious biofilms to dispersants induces high bacterial concentrations in blood that may cause sepsis. Preventing sepsis requires simultaneous biofilm dispersal and bacterial killing. Here, self-targeting DCPA(2-(4-((1,5-bis(octadecenoyl)1,5-dioxopentan-2-yl)carbamoyl)pyridin-1-ium-1-yl)acetate) liposomes with complexed water were self-assembled with ciprofloxacin loaded in-membrane and PEGylated as a lipid-membrane component, together with bromelain loaded in-core. Inside biofilms, DCPA-H 2 O and PEGylated ciprofloxacin became protonated, disturbing the balance in the lipid-membrane to cause liposome-burst and simultaneous release of bromelain and ciprofloxacin. Simultaneous release of bromelain and ciprofloxacin enhanced bacterial killing in Staphylococcus aureus biofilms as compared with free bromelain and/or ciprofloxacin. After tail-vein injection in mice, liposomes accumulated inside intra-abdominal staphylococcal biofilms. Subsequent liposome-burst and simultaneous release of bromelain and ciprofloxacin yielded degradation of the biofilm matrix by bromelain and higher bacterial killing without inducing septic symptoms as obtained by injection of free bromelain and ciprofloxacin. This shows the advantage of simultaneous release from liposomes of bromelain and ciprofloxacin inside a biofilm.
研究领域:
医学
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药理学
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生物材料
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Huijing Cong,Jing Hu,Jing Wang,Baiyu Chang,Rongtao Li,Xinran Cui,Chenghao Zhang,Hongyu Ji,Congcong Lin,Jingling Tang,Jiaxin Liu
Parkinson’s disease confronts challenges in drug delivery due to the blood-brain barrier. Intranasal delivery bypasses the blood-brain barrier for improved drug bioavailability, yet narrow nasal space and brief retention time hinder clinical applicability. We conducted a Bromocriptine Mesylate-loaded PLGA nanoparticles co-modified with low molecular weight protamine (LMWP) and lactoferrin (Lf) (LMWP/Lf-BCM-NPs) for nose-to-brain delivery. The resulting LMWP/Lf-BCM-NPs were uniform spheres with an average size of 248.53 ± 16.25 nm and zeta potential of −2.63 ± 0.74 mV. Fourier transform infrared spectroscopy confirmed LMWP and Lf attachment. The co-modified nanoparticles showed improving cellular transport and good viability. The LMWP/Lf-BCM-NPs showed increased brain targeting efficiency in mice. In haloperidol-induced Parkinson mouse models, the LMWP/Lf-BCM-NPs showed increased brain targeting efficiency, enhanced behavioral regulatory effects, enhanced antioxidant effects and neuroprotection effects. This study paves the way for a novel, non-invasive brain-targeted therapy, offering a promising avenue for Parkinson’s disease clinical treatment.
研究领域:
药剂学
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神经科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2022
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IF 5.195
Xin Liu,Zhao-Yan Cheng,Yan-Feng Li,Chao Liu,Chen Wang,Xiao-Jian Gong,Ling He
Alzheimer's Disease (AD) is the most common neurodegenerative disease , which lacks disease-modifying therapeutics so far. Studies have shown that the dysfunction of the dopaminergic system is related to a variety of pathophysiology of AD, and the expression of Dopamine D2 receptor (DRD2) in the brains of AD patients and animal models is significantly downregulated, suggesting that DRD2 may represent a therapeutic target for AD. However, the strategy of targeting DRD2 for AD treatment still lacks some key experimental evidences. Here we show that DRD2 agonist Bromocriptine improved Aβ 1-42 induced neuroinflammation , neuronal apoptosis , and memory deficits in mice. For animal study, the mice have injected intracerebroventricularly (i.c.v.) with Aβ 1-42 (410 pmol/5 μl) to induced AD cognitive deficit model (Mazzola et al., 2003; van der Stelt et al., 2006). After 7 days, Bromocriptine (2.5 mg/kg, 5 mg/kg and 10 mg/kg) or normal saline was administered intragastrically once a day for 30 days. Behavioral tests about the Y maze and Morris water maze in mice were initiated on the twenty-fourth day of drug administration for 7 days. In vivo and in vitro mechanism research revealed that Bromocriptine, via activating DRD2, promoted the recruitment of PP2A and JNK by scaffold protein β-arrestin 2, that repressed JNK-mediated transcription of proinflammatory cytokines and activation of NLRP3 inflammasome in microglia . Collectively, our findings suggest that Bromocriptine can ameliorate Aβ 1-42 induced neuroinflammation and memory deficits in mice through DRD2/β-arrestin 2/PP2A/JNK signaling axis, which provides an experimental basis for the development of Bromocriptine as a drug for AD.
研究领域:
神经科学
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药理学
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
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