JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Zhongyi Ma,Xinlong Liu,Xinyu Xie,Yike Fang,Dingxi Jiang,Chen Zhao,Pingrong Li,Yu Fu,Lianghong Ye,Yuan Gao,Shuang Wu,Chong Li
Overcoming the challenges associated with brain-targeted drug delivery involves addressing both the limited biodistribution of drugs and microcirculation issues that hinder their accumulation in brain lesions. In this study, we propose a comprehensive strategy leveraging vinpocetine, a compound known to enhance cerebral blood flow (CBF), to improve drug delivery to the brain. Initially, the pre-administration of vinpocetine in the form of a microemulsion significantly enhances nanomedicine uptake into the brain by selectively boosting CBF. This creates a more favorable environment for drug distribution while also mitigating chemotherapy-induced cerebrovascular accidents. Building upon this, the use of vinpocetine as a targeting ligand for liposomes or lipid nanoparticles, compared to typical brain-targeting ligands (GSH, Apamin, and Angiopep-2), not only significantly improves drug distribution in the brain but also selectively targets glioma regions and maintains excellent immunocompatibility. Expanding on these findings, the direct conjugation of vinpocetine with therapeutic compounds leads to superior brain accumulation and enhanced antitumor efficacy, thereby extending its therapeutic potential. These results highlight the broad applicability of vinpocetine-based strategies for achieving efficient and precise brain-targeted drug delivery, offering promising prospects for treating a range of central nervous system disorders.
研究领域:
药理学
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神经科学
·
生物医学工程
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2010
·
IF 6.401
Keri A. Barksdale,Emma Perez-Costas,Johanna C. Gandy,Miguel Melendez-Ferro,Rosalinda C. Roberts,Gautam N. Bijur
Neuronal function in the brain requires energy in the form of ATP, and mitochondria are canonically associated with ATP production in neurons. The electrochemical gradient, which underlies the mitochondrial transmembrane potential (ΔΨ mem ), is harnessed for ATP generation. Here we show that ΔΨ mem and ATP-production can be engaged in mitochondria isolated from human brains up to 8.5 h postmortem. Also, a time course of postmortem intervals from 0 to 24 h using mitochondria isolated from mouse cortex reveals that ΔΨ mem in mitochondria can be reconstituted beyond 10 h postmortem. It was found that complex I of the mitochondrial electron transport chain was affected adversely with increasing postmortem intervals. Mitochondria isolated from postmortem mouse brains maintain the ability to produce ATP, but rates of production decreased with longer postmortem intervals. Furthermore, we show that postmortem brain mitochondria retain their ΔΨ mem and ATP-production capacities following cryopreservation. Our finding that ΔΨ mem and ATP-generating capacity can be reinitiated in brain mitochondria hours after death indicates that human postmortem brains can be an abundant source of viable mitochondria to study metabolic processes in health and disease. It is also possible to archive these mitochondria for future studies.—Barksdale, K. A., Perez-Costas, E., Gandy, J. C., Melendez-Ferro, M., Roberts, R. C., Bijur, G. N. Mitochondrial viability in mouse and human postmortem brain.
研究领域:
神经科学
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细胞生物学
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代谢研究
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DOI
PubMed
高影响因子
Fundamental Research
·
2025
·
IF 6.3
Dandan Kou,Keyang Xu,Jiahui Yin,Ning Wang,Ruru Zhang,Jianfeng Zeng,Mingyuan Gao
The development of sustainable and non-invasive method for delivering drugs to the brain is crucial for the effective treatment of Parkinson’s disease (PD). In this study, nanoparticles were formulated by using poly (ethylene glycol)-block-poly (propylene glycol)-block-poly (ethylene glycol) (PEG- b -PPG- b -PEG) to facilitate an efficient intranasal delivery of rotigotine directly into the brain. It was found that the intranasal route enabled more effective accumulation of rotigotine in the brain than conventional intravenous administration, demonstrating its feasibility as an innovative delivery approach for PD treatment. Furthermore, the behavioral test, brain histology and immunochemistry analyses demonstrated a significant improvement in the symptoms of PD-like neurodegeneration in mice treated with intranasally delivered rotigotine-loaded nanoparticles. These outcomes affirm an outstanding therapeutic efficacy of the nano-formulation for intranasal delivery, highlighting its potential for the effective treatment of neurodegenerative disorders, particularly PD.
研究领域:
神经科学
·
药物递送
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2017
·
IF 6.402
Xiao Hu,Feifei Yang,Yonghong Liao,Lin Li,Lan Zhang
This study investigated cholesterol–polyethylene glycol (PEG) comodified poly (ethyleneglycol)-poly (lactide) nanoparticles (CLS-PEG NPs) as a novel, biodegradable brain drug delivery system and included an evaluation of its in vitro and in vivo properties. To this end, coumarin-6 (C6), a fluorescent probe, was encapsulated into CLS-PEG NPs by an emulsion polymerization method. We reported that the use of CLS-PEG NPs led to a sustained drug release in vitro. Additionally, cell viability experiments confirmed their safety. The uptake and transport of CLS-PEG NPs, by bEnd.3 cells (an immortalized mouse brain endothelial cell line), was significantly higher than that of a control C6 solution. An investigation of the uptake mechanisms of different NP formulations demonstrated that cholesterol modifications may be the primary way to improve the efficiency of cellular uptake, wherein macropinocytosis may be the most important endocytic pathway in this process. An investigation of the transport mechanisms of CLS-PEG NPs also implicated macropinocytosis, energy and cholesterol in bEnd.3 cells lines. Following an intravenous (IV) administration to rats, pharmacokinetic experiments indicated that C6-loaded CLS-PEG NPs achieved sustained release for up to 12 h. In addition, IV delivery of CLS-PEG NPs appeared to significantly improve the ability of C6 to pass through the blood–brain barrier: the concentration of C6 found in the brain increased nearly 14.2-fold when C6 CLS-PEG NPs were used rather than a C6 solution. These in vitro and in vivo results strongly suggest that CLS-PEG NPs are a promising drug delivery system for targeting the brain, with low toxicity.
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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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Chenjie Xia,Changhui Hu,Rui Xu,Feihong Zhuo,Mengfei Yang,Yinjia Li,Zixuan Shan,Cheng Xu,Yutong Wang,Zhipeng Chen
Ischemic stroke is a neurological disease characterized by high morbidity and mortality. A key pathological mechanism involves rapid restoration of blood oxygen in the infarcted area, which triggers oxidative stress and inflammatory responses leading to neuronal damage. The complex etiology of the disease poses challenges to single-target pharmacotherapy, necessitating the development of multi-targeted combination drug treatments. Reports showed that water- and lipid-soluble components of Danshen, exert synergistic neuroprotective effects. However, the disparate physicochemical properties of these compounds lead to differential release kinetics, hampering the therapeutic efficacy. Furthermore, the blood-brain barrier (BBB) presents a formidable obstacle to the penetration of water-soluble constituents. Here, we developed a novel biomimetic drug delivery system utilizing hollow polydopamine coated with red blood cell membranes. Water-soluble (W) and lipid-soluble (L) components of Danshen were loaded at distinct membrane regions to facilitate synchronized release profile. Additionally, borneol was used to modify the membrane to enhance the BBB penetration capacity. Mechanism study revealed that W and L possess synergistic effect through inhibiting NF-κB and TNF-α pathways. In summary, this delivery system enables concurrent loading and efficient brain delivery of multiple constituents, thereby promoting neurological recovery and presenting a promising therapeutic strategy for ischemic stroke.
研究领域:
神经病学
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药剂学
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药理学
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生物医学工程
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神经科学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Zhiguo Lu,Ruichen Zhao,Yi Li,Jianze Wang,Jing Guo,Chaobo Bai,Jing Chen,Jun Yang,Yiwan Geng,Tianlu Zhang,Yanyue Wu,Xiyue Jiao,Yining Wang,Junliang Yuan,Xin Zhang
Reactive oxygen species (ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders. The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system. However, ROS under redox homeostasis regulates a wide range of life activities. Therefore, smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely. This study reports a smart antioxidant function enhancement (SAFE) strategy. On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system, thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner. Through structural modulation and ligand modification, we develop SAFE nanoparticles based on nanohybrid complexes (SAFE-complex) adapted to brain delivery of nucleic acid drugs. SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage. Moreover, SAFE-complex can stabilize storage in the form of freeze-dried powder. These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.
研究领域:
药理学
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纳米技术
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神经科学
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分子生物学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2013
·
IF 2.987
Xiao Zhang,Gang Chen,Lu Wen,Fan Yang,A-li Shao,Xia Li,Wei Long,Lei Mu
The aim of this study was to develop novel multiple agents loaded poly ( d , l -lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) and evaluate their potential for brain delivery via inner ear administration. PLGA NPs loaded with salvianolic acid B (Sal B), tanshinone IIA (TS IIA) and panax notoginsenoside (PNS) were prepared by double emulsion/solvent evaporation method. It was observed that optimized NPs displayed satisfactory encapsulation efficiency and desired sustained-release characteristics. NPs following intratympanic administration (IT) in guinea pigs greatly improved drug distribution within the inner ear, cerebrospinal fluid (CSF) and brain tissues compared with intravenous administration (IV). Pharmacodynamic studies demonstrated that NPs following IT markedly inhibited oxidizing reactions and protected the brain from cerebral ischemia reperfusion (I/R) injury by upregulating superoxide dismutase (SOD) activity both in serum and brain tissues, simultaneously significantly reducing the levels of malondialdehyde (MDA) and nitric oxide synthase (NOS). Moreover intratympanic delivery did not cause injury of cochlear function by preliminary study on the toxicity. These findings suggested that PLGA NPs-based delivery system via inner ear administration was a promising candidate to brain delivery for the treatment of brain diseases.
研究领域:
药剂学
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神经科学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
REGULATORY TOXICOLOGY AND PHARMACOLOGY
·
2025
·
IF 3.5
Liqiang Gu,Yanping Hu,Yinfang Lai,Sheng Zhang,Haoran Wang,Xiaozhen Xu,Lingfang Chen,Yuhua Shi,Jiechao Chen,Xiaochun Sun,Yuan Zhang,Lingzhi Hu
Bioequivalence test is typically conducted by determining the drug concentration in plasma. However, this is not suitable for brain drugs (like Edaravone) that have targets in CNS. The amount of a drug in target site in the CNS is responsible for its activity in the brain, while the concentration of a drug in the blood has a weak impact on the CNS. In this paper, a new consistency evaluation method for brain drugs was established. 16 rats were divided into two groups. One group was administered the test preparation, and the other group was administered the control preparation. Then, cerebrospinal fluid (CSF) samples were collected. All of the CSF samples were examined by LC-MS. The 90 % confidence interval of the geometric mean ratio of AUC 0-t was 90.30–150.59 %, and 91.79–211.06 % for C max . In addition, the result indicated that the two preparations were not bioequivalent in the CNS, although the concentration-time profile and pharmacokinetic parameters were quite similar. The results revealed the particularity and complexity of the bioequivalence test for brain drugs that have targets in the CNS. The feasibility of the test was confirmed, and our results provide useful information for the consistency evaluation of brain drugs.
研究领域:
药理学
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神经科学
·
药物研究
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分析化学
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药物开发
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Fangyuan Wang,Zhuanzhuan Yang,Mengli Liu,Yaotian Tao,Zhenbao Li,Zonghao Wu,Shuangying Gui
A rotigotine (ROT)-loaded polymer micelles thermosensitive gel (ROT-PM-TSG) delivery system was engineered to enhance the solubility of the drug, prolong the residence time, and increase the concentration of the drug in the brain tissue. First, ROT-loaded polymer micelles (ROT-PM) were tailored and optimized. The average particle size, encapsulation efficiency, and drug loading of the ROT-PM were (88.62 ± 1.47) nm , (93.5 ± 0.79) %, and (19.9 ± 0.60) %. The optimal ROT-PM-TSG formulation contained 22% P407 and 2% P188 with a gelation temperature of about 32.3 °C and a pH of 5.186. In vivo , the MRT of ROT-PM and ROT-PM-TSG nasal administration was 1.43 and 1.79 times extended than that of the intravenous. In comparison with the intravenous group, the distribution of ROT in olfactory bulb, cerebrum , cerebellum and striatum was 276.6%, 170.5%, 166.5% and 184.4%, respectively. In conclusion, the ROT-PM-TSG system has proven to be a potential application prospect as a ROT nose-to-brain delivery system.
研究领域:
药剂学
·
药物递送系统
·
神经药理学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Wenqin Yang,Yulong Shi,Yiwei Zhang,Yating Yang,Yufan Du,Zixiao Yang,Xiaorong Wang,Ting Lei,Yanyan Xu,Yongke Chen,Fan Tong,Yazhen Wang,Qianqian Huang,Chuan Hu,Huile Gao
The unsatisfactory treatment outcome of Alzheimer’s disease (AD) can be attributed to two primary factors, the intricate pathogenic mechanisms leading to restricted treatment effectiveness against single targets and the hindered drug accumulation in brain due to blood–brain barrier obstruction. Therefore, we developed a carrier-free nanomodulator (NanoDS) through the self-assembly of donepezil and simvastatin for direct nose-to-brain delivery. This approach facilitated a rapid and efficient traversal through the nasal epithelial barrier, enabling subsequent drug release and achieving multiple therapeutic effects. Among them, donepezil effectively ameliorated the symptoms of AD and restored synaptic plasticity. Simvastatin exerted a neurotrophic effect and facilitated the clearance of amyloid-β aggregation. At the same time, NanoDS demonstrated effective anti-inflammatory and antioxidative stress effects. This therapy for AD is approached from both symptomatic and etiological perspectives. In the treatment of FAD4T transgenic mice, it highly improved spatial memory impairment and cognitive deficits while restoring the homeostasis of brain microenvironment. Collectively, our study presented a paradigm for both achieving efficient brain delivery and offering pleiotropic therapies for AD.
研究领域:
神经科学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomedical Optics Express
·
2018
·Vol. 9
·期 10
·4850-4862
·
IF 3.482
Chao Zhang,Wei Feng,Elena Vodovozova,Daria Tretiakova,Ivan Boldyrevd,Yusha Li,Jurgen Kürths,Tingting Yu,Oxana Semyachkina-Glushkovskaya,Dan Zhu
The photodynamic (PD) effect has been reported to be efficient for the opening of the blood-brain barrier (BBB), which provides a new informative platform for developing perspective strategies towards brain disease therapy and drug delivery. However, this method is usually performed via craniotomy due to high scattering of the turbid skull. In this work, we employed a newly-developed optical clearing skull window for investigating non-invasive PD-induced BBB opening to high weight molecules and 100-nm fluid-phase liposomes containing ganglioside GM1. The results demonstrated that the BBB permeability to the Evans blue albumin complex is related to laser doses. By in vivo two-photon imaging and ex vivo confocal imaging with specific markers of the BBB, we noticed PD-related extravasation of rhodamine-dextran and liposomes from the vessels into the brain parenchyma. The PD induced an increase in oxidative stress associated with mild hypoxia and changes in the expression of tight junction (CLND-5 and ZO-1) and adherens junction (VE-cadherin) proteins, which might be one of the mechanisms underlying the PD-related BBB opening for liposomes. Our experiments indicate that optical clearing skull window will be a promising tool for non-invasive PD-related BBB opening for high weight molecules and liposomes that provides a novel useful tool for brain drug delivery and treatment of brain diseases.
研究领域:
神经科学
·
药理学
·
生物医学工程
·
光学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2020
·
IF 2.734
Rui Bao,Qi-Long Wang,Ran Li,Michael Adu-Frimpong,Elmurat Toreniyazov,Hao Ji,Xi-Ming Xu,Jiang-Nan Yu
6-Shogaol is one component of ginger, which has been described to possess various health-promoting effects including anticancer, antiinflammatory, antioxidant and antiatherogenic. However, poor water solubility has limited the aforementioned health benefits and clinical applications of the drug. Herein, the aforementioned drawback was circumvented by the preparation of 6-shogaol-loaded liposome through thin-film dispersion method with TPGS as the carrier, in comparison with 6-shogaol liposome and free 6-shogaol. Appropriate indices were used for the characterization of the developed liposomes viz., particle size (PS), zeta potential (Z-potential), polydispersity index (PDI), entrapment efficiency (EE) and loading capacity (LC) while their morphologies were observed under the transmission electron microscopy (TEM). In-vitro dissolution investigation showed a substantial improvement in the accumulative release rates of liposomes comparable to the free 6-shogaol. The TPGS-modified 6-shogaol and 6-shogaol liposomes had oral relative bioavailability (RBA) of 580.04% and 281.55%, respectively, with improved t 1/2 , MRT, C max , AUC 0-t and T max . Pertinently, the TPGS coated 6-shogaol liposome may enhance the targeting of the drug to the brain. Therefore, the TPGS coated 6-shogaol liposome could potentially improve oral bioavailability of lipophilic drug in-vivo . More importantly, the results of tissue distribution investigation suggest that TPGS coated 6-shogaol liposome may act as promising carrier for brain delivery in future.
研究领域:
药剂学
·
药理学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）