ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Tongkai Chen,Wei Liu,Sha Xiong,Dongli Li,Shuhuan Fang,Zhenfeng Wu,Qi Wang,Xiaojia Chen
Recent work has highlighted the potential of puerarin (PU) as a valuable compound to treat Parkinson’s disease (PD), but its undesirable water solubility and bioavailability have constrained its utility. In this study, we sought to develop nanoparticles (NPs) that could be used to encapsulate PU, thereby extending its in vivo half-life and improving its bioavailability and accumulation in the brain to treat the symptoms of PD. We prepared spherical NPs (88.36 ± 1.67 nm) from six-armed star-shaped poly(lactide-co-glycolide) (6-s-PLGA) NPs that were used to encapsulate PU (PU-NPs) with 89.52 ± 1.74% encapsulation efficiency, 42.97 ± 1.58% drug loading, and a 48 h sustained drug release. NP formation and drug loading were largely mediated by hydrophobic interactions, while changes in the external environment led these NPs to become increasingly hydrophilic, thereby leading to drug release. Relative to PU alone, PU-NPs exhibited significantly improved cellular internalization, permeation, and neuroprotective effects. Upon the basis of Förster resonance energy transfer (FRET) of NPs-administered zebrafish, we were able to determine that these NPs were rapidly absorbed into circulation whereupon they were able to access the brain. We further conducted oral PU-NPs administration to rats, revealing significant improvements in PU accumulation within the plasma and brain relative to rats administered free PU. In MPTP-mediated neurotoxicity in mice, we found that PU-NPs treatment improved disease-associated behavioral deficits and depletion of dopamine and its metabolites. These findings indicated that PU-NPs represent a potentially viable approach to enhancing PU oral absorption, thus improving its delivery to the brain wherein it can aid in the treatment of PD.
研究领域:
药剂学
·
神经科学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2022
·Vol. 18
·期 2
·571-580
·
IF 3.641
Zhou Shuwen,Zheng Xinmeng,Chen Jun,Xu Yiyang,Du Xuancheng,Wang Cheng,Cui Pengfei,Qiu Lin,Jiang Pengju,Ni Xinye,Wang Jianhao
Intranasal administration, which can bypass the blood–brain barrier (BBB), is widely recognized as a promising strategy for high-efficiency drug delivery to the brain. Herein, for the purpose of effectively delivering drugs to the brain via intranasal administration, glutathione
(GSH)-modified gellan gum (GSH-GG) with ion/temperature dual responsive properties was synthesized and encapsulated on galanthamine hydrobromide (GH)-loaded liposomes (GH-Lipo) for effective GH delivery to the brain (GH-Lipo@GSH-GG). Our results demonstrated that GSH-GG greatly decreased the
gelation temperature of GG from 44.0 °C to 22.1 °C without compromising its ion responsiveness. Moreover, GSH-GG had a good protection ability for GH-loaded liposomes without affecting its drug release. Most importantly, the finally obtained GH-Lipo@GSHGG showed acceptable targeted
delivery of GH to the brain upon in vivo administration. Therefore, this formulation can be employed as a potential delivery system in nasal-to-brain delivery.
研究领域:
药剂学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Luting Wang,Lin Xu,Junfeng Du,Xiao Zhao,Mei Liu,Jianfang Feng,Kaili Hu
Targeted treatment of cerebral ischemia/reperfusion injury (CIRI) remains a problem due to the difficulty in drug delivery across the blood–brain barrier (BBB). In this study, we developed Bo-TSA-NP, a novel tanshinone IIA (TSA) loaded nanoparticles modified by borneol, which has long been proved with the ability to enhance other drugs’ transport across the BBB. The Bo-TSA-NP, with a particle size of about 160 nm, drug loading of 3.6%, showed sustained release and P-glycoprotein (P-gp) inhibition property. It demonstrated a significantly higher uptake by 16HBE cells in vitro through the clathrin/caveolae-mediated endocytosis and micropinocytosis. Following intranasal (IN) administration, Bo-TSA-NP significantly improved the preventive effect on a rat model of CIRI with improved neurological scores, decreased cerebral infarction areas and a reduced content of malondialdehyde (MDA) and increased activity of superoxide dismutase (SOD) in rat brain. In conclusion, these results indicate that Bo-TSA-NP is a promising nose-to-brain delivery system that can enhance the prevention effect of TSA on CIRI.
研究领域:
药剂学
·
神经科学
·
药物递送系统
✓ 已验证
DOI
高影响因子
RARE METALS
·
2025
·
IF 11
Deng Shu-Yue,Zhou Xin-Yu,Zou Xiao-Peng,Tang Fang,Yang Dong,Sun Cai-Xia,Luo Jun,Ge Xing,Zhu Jia-Ying,Fang Tian-Ye,Yue Cai-Feng,Ju Yan-Min,Dai Jian-Jun
The presence of the blood–brain barrier limits the drug concentration in the brain, while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance, making the clinical treatment of bacterial meningitis challenging. Herein, a nose-to-brain delivery strategy of small-sized nanozyme has been fabricated for combating bacterial meningitis, to overcome the low drug concentration and drug resistance. This strategy was achieved by a protein-supported Au nanozyme (ANZ). With a particle size of less than 10 nm, it possesses both glucose oxidase-like and peroxidase-like activities and can generate large amounts of reactive oxygen species through a cascade effect without the addition of external H 2 O 2 . Benefiting from the cascade catalytic amplification effect generated by its dual enzyme-like activities, ANZ shows significant broad-spectrum antibacterial activity without inducing bacterial resistance in vitro. Notably, small-sized ANZ exhibits higher brain entry efficiency and greater accumulation after intranasal administration compared to oral or intravenous administration. In a mouse model of bacterial meningitis, the mice treated with ANZ had lower bacterial loads in the brain and higher survival and clinical behavior scores compared to the classical antibiotic ceftriaxone. Additionally, the meningitis mice exhibited undamaged cognitive and behavioral abilities, indicating the excellent biocompatibility of ANZ. The above results demonstrate that nose-to-brain delivery of ANZ exhibits high intracerebral accumulation, strong antibacterial efficacy and does not lead to bacterial resistance. It holds broad prospects for the treatment of bacterial meningitis. Graphical abstract
研究领域:
医学
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药理学
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纳米医学
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产品关联
DOI
高影响因子
Drug Delivery and Translational Research
·
2017
·Vol. 8
·期 1
·83-96
·
IF 3.094
Pan Linmei,Zhou Jing,Ju Feng,Zhu Huaxu
Alpha-asarone is a bioactive component of Acorus tatarincuii Schott with low bioavailability, which is often used for treatments of various brain diseases in clinical setting. This study was to formulate biodegradable methoxy polyethylene glycol-polylactic acid (mPEG-PLA) nanoparticles (NPs) surface-modified by lactoferrin (Lf), for delivering α-asarone into the brain following intranasal administration. Alpha-asarone NPs were prepared by premix membrane emulsification. The relative parameters were optimized by a Box-Behnken experimental design. The particle size, zeta potential, and dispersibility index of NPs and Lf-NPs were characterized. Their ex vivo permeation, pharmacokinetics, distribution in the brain and other tissue, brain targeting, and toxicity were investigated. Following intranasal administration, Lf-NPs had a better permeability and no significant poor bioavailability compared to NPs; the area under curve from 0 to 12 h of α-asarone in Lf-NPs of the olfactory bulb, hippocampus, olfactory bundles, and thalamus were 2.14-, 4.17-, 3.62-, and 1.96-fold of those in NP group, respectively. Lactoferrin could enhance the efficacy of brain targeting with NPs and reduce its liver accumulation. Toxicity of NPs on nasal mucosal cilia and epithelial cells was also decreased by Lf. To summarize, these results demonstrate that Lf-NPs of α-asarone have potential as a carrier for nose-to-brain delivery of α-asarone for brain diseases.
研究领域:
药剂学
·
神经科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SAUDI PHARMACEUTICAL JOURNAL
·
2023
·
IF 4.1
Maryam H. Alaayedi,Nidhal K. Maraie
Nose-to-brain delivery allows the direct targeting of drug molecules bypassing the Blood Brain Barrier and systemic effect. Nanoemulsion is one of the novel strategies to deliver drug in this route due to its simplicity in manufacturing, long-term stability, and strong solubilization property for drug. The anticancer drug lomustine had poor oral bioavailability in addition to its serious side effect, therefore, developing more effective drug delivery with direct targeting towards the brain through intra-nasal administration applying nanoemulsion technology is a promising alternative. The work involved lomustine solubility screening in oils, surfactants and cosurfactants as well as emulsifier ratio (Smix) nanoemulsion area was identified using pseudo-ternary phase diagrams. Eighteen nanoemulsion formulas were produced for optimization, then characterized for droplet size, polydispersity index, zeta potential, entrapment efficiency, conductivity, transmittance, dilution, visual transparency, physical stability and in vitro release. The optimum NE formula showed droplet size, zeta potential, polydispersity index, entrapment efficiency, %transmittance, conductivity of 31.31 nm, −30.65 mV, 0.159, 98.12%, 99.08%, and 951 us/cm, respectively. The best formula released 100% lomustine within 15 min which is a promising potential drug delivery system that may deliver the drug quickly and directly to the brain as a safe and effective alternative to oral delivery.
研究领域:
药剂学
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肿瘤学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Yanyan Xu,Xiangtong Ye,Yanfeng Du,Wenqin Yang,Fan Tong,Wei Li,Qianqian Huang,Yongke Chen,Hanmei Li,Huile Gao,Weiwei Zhang
Alzheimer’s disease (AD), characterized by β -amyloid (A β ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α -mangostin ( α -M) and β -site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α -M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting A β production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α -M reversed A β -induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of A β , while siB effectively suppressed BACE1 expression, abrogating A β synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial A β plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.
研究领域:
神经科学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 13
·4765-4777
·
IF 6.843
Shu Li,Chen Guo,Xingjiao Zhang,Xiaojing Liu,Jing Mu,Chunxia Liu,Yali Peng,Min Chang
Anxiety disorders are the most common mental diseases and can greatly disrupt everyday life. Although there has been substantial research on anxiety disorders, novel therapeutics are needed. Neuropeptide S (NPS) is a potential therapeutic candidate owing to its strong anxiolytic activity; however, some disadvantages, such as its poor metabolic stability and inability to cross the blood–brain barrier (BBB), limit its use in the clinic. Herein, inspired by nose-to-brain drug delivery strategies, an endogenous 20-amino-acid-long mNPS peptide was modified by incorporating palmitic acid into its functional Lys12 side chain (M-3), which was expected to facilitate nose-to-brain penetration and exert a prolonged anxiolytic-like effect compared to mNPS. We found that M-3 assembled into nanofibers that retained the bioactivity of NPS and exhibited obvious improvements in metabolic stability. Notably, as expected, self-assembled M-3 was able to penetrate into the brain and exert anxiolytic effects. The elevated plus-maze (EPM) results further revealed that M-3 could produce prolonged anxiolytic-like effects in mice. In vivo imaging studies revealed that self-assembled M-3 could be efficiently transported from the nasal cavity to the brain. Furthermore, when intranasally administered, this molecule exhibited a significantly prolonged anxiolytic-like effect, which further illustrated that this molecule has a potent nose-to-brain penetration in vivo. Overall, this self-assembled nanofiber showed potent nose-to-brain penetration ability and prolonged bioactivity.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 2
·635
·
IF 4.6
Yinfang Lai,Liping Hua,Jiali Yang,Juewen Xu,Junduo Chen,Shuangshuang Zhang,Shunyao Zhu,Jingjing Li,Senlin Shi
Objective: To study the extraction process of agarwood active ingredients (AA) and investigate the safety and effectiveness of AA in the treatment of insomnia rats by nasal administration. Method: A β-cyclodextrin (β-CD) inclusion compound (a-β-CD) was prepared from agarwood essential oil (AEO), and the preparation process was optimized and characterized. The safety of AA in nasal mucosa was evaluated throughBufo gargarizansmaxillary mucosa and rat nasal mucosa models. Insomnia animal models were replicated by injectingp-chlorophenylalanine (PCPA), conducting behavioral tests, and detecting the expression levels of monoamine neurotransmitters (NE and 5-HT) and amino acids (GABA/Glu) in the rat hypothalamus. Results: The optimum inclusion process conditions of β-CD were as follows: the feeding ratio was 0.35:1.40 (g:g), the inclusion temperature was 45 °C, the inclusion time was 2 h, and the ICY% and IEO% were 53.78 ± 2.33% and 62.51 ± 3.21%, respectively. The inclusion ratio, temperature, and time are the three factors that have significant effects on the ICY% and IEO% of a-β-CD. AA presented little damage to the nasal mucosa. AA increased the sleep rate, shortened the sleep latency, and prolonged the sleep time of the rats. The behavioral test results showed that AA could ameliorate depression in insomnia rats to a certain extent. The effect on the expression of monoamine neurotransmitters and amino acids in the hypothalamus of rats showed that AA could significantly reduce NE levels and increase the 5-HT level and GABA/Glu ratio in the hypothalamus of insomnia rats. Conclusion: The preparation of a-β-CD from AEO can reduce its irritation, improve its stability, increase its curative effect, and facilitate its storage and transport. AA have certain therapeutic effects on insomnia. The mechanism of their effect on rat sleep may involve regulating the expression levels of monoamine neurotransmitters and amino acids in the hypothalamus.Keywords:agarwood;supercritical fluid extraction;β-cyclodextrin;nose-to-brain delivery;insomnia
研究领域:
药理学
·
神经科学
·
药剂学
·
中医中药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2024
·
IF 2.6
Chunqing Wang,Xin Huang,Ziyan Tang,Yizhi Zhang,Meng Wei,Shumin Du,Xingshuang Song,Yanping Wu,Qiang Chi,Xiaomei Zhuang,Du Lina,Yiguan Jin
Sleep disorders are one of the most common acute reactions on the plateau, which can cause serious complications. However, there is no effective and safe treatment currently available. Nimodipine (NMD) is a dihydropyridine calcium channel blocker with neuroprotective and vasodilating activity, mainly used for the treatment of ischemic brain injury. Commercial oral or injectable NMD formulations are not a good option for central neuron diseases due to their poor brain delivery. In this study, nimodipine dissolving microneedles (NDMNs) were prepared for the prevention of sleep disorders caused by hypoxia. NDMNs were composed of NMD and polyvinyl pyrrolidone (PVP) K90 with a conical morphology and high rigidity. After administration of NDMNs on the back neck of mice, the concentration of NMD in the brain was significantly higher than that of oral medication as was confirmed by the fluorescent imaging on mouse models. NDMNs enhanced cognitive function, alleviated oxidative stress, and improved the sleep quality of mice with high-altitude sleep disorders. The blockage of calcium ion overloading may be an important modulation mechanism. NDMNs are a promising and user-friendly formulation for the prevention of high-altitude sleep disorders.
研究领域:
药理学
·
神经科学
·
睡眠医学
·
高原医学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Liuxiang Chu,Aiping Wang,Ling Ni,Xiuju Yan,Yina Song,Mingyu Zhao,Kaoxiang Sun,Hongjie Mu,Sha Liu,Zimei Wu,Chunyan Zhang
Glioblastoma is the most common malignant brain tumor. Efficient delivery of drugs targeting glioblastomas remains a challenge. Ephrin type-A receptor 3 (EPHA3) tyrosine kinase antibody-modified polylactide-co-glycolide (PLGA) nanoparticles (NPs) were developed to target glioblastoma via nose-to-brain delivery. Anti-EPHA3-modified, TBE-loaded NPs were prepared using an emulsion-solvent evaporation method, showed a sustained in vitro release profile up to 48 h and a mean particle size of 145.9 ± 8.7 nm. The cellular uptake of anti-EPHA3-modified NPs by C6 cells was significantly enhanced compared to that of nontargeting NPs (p < .01). In vivo imaging and distribution studies on the glioma-bearing rats showed that anti-EPHA3-modified NPs exhibited high fluorescence intensity in the brain and effectively accumulated to glioma tissues, indicating the targeting effect of anti-EPHA3. Glioma-bearing rats treated with anti-EPHA3-modified NPs resulted in significantly higher tumor cell apoptosis (p < .01) than that observed with other formulations and prolonged the median survival time of glioma-bearing rats to 26 days, which was 1.37-fold longer than that of PLGA NPs. The above results indicated that anti-EPHA3-modified NPs may potentially serve as a nose-to-brain drug carrier for the treatment of glioblastoma.
研究领域:
神经学
·
药剂学
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Yang Xu,Ge Yan,Jingyu Zhao,Yunhao Ren,Qiyao Xiao,Minhong Tan,Lihua Peng
Cell heterogeneous nanomaterials based therapeutic strategies for Parkinson’s disease (PD) have been widely investigated, however, challenged by the potential toxicity, immunogenicity, limited drug loading efficiency, and restricted penetration through biological barriers. Herein, for the first time, a medicinal plant, Pueraria lobata derived exosomes (Pu-Exos) were demonstrated with excellent capability in overcoming cellular membrane and endosomal barriers, ensuring the efficient delivery of incorporated biomacromolecule cargos to SH-SY5Y cells. Upon that, Pu-Exos comprehensively improved the mitochondrial dysfunction of SH-SY5Y cells through removing dysfunctional mitochondria via PINK1-Parkin mediated mitophagy, and restoring ATP supplementation by preserving the activities of mitochondrial respiratory chain complexes I and V. Pu-Exos were then engineered with the ternary ligand, DSPE-PEG-RVG, forming Pu-Exos-PR that were further optimized for the cellular uptake and brain enrichment in vivo , therefore excellently promoting the survival of dopaminergic neurons, with reduced cellular degeneration, denser Nissl substance and increased tyrosine hydroxylase expression, accompanied by obviously alleviated motor and non-motor symptoms. Pu-Exos-PR were shown as a promising exosome with outstanding biocompatibility, efficient incorporation of bioactive agents, and unique feature in penetration through both nasal tissue and blood brain barrier, inaugurating new avenues to brain-targeting delivery for biomacromolecules for PD therapy. This study also casts new insight on the plant-derived exosomes as next generation of cell homogenous nanoplatforms with high efficiency and biosafety for drug delivery and therapy of brain diseases.
研究领域:
神经科学
·
药学
·
分子生物学
·
生物技术
✓ 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）