International Journal of Nanomedicine
·
2025
·
IF 6.5
Guangzhe Xu,Chun Ma,Hongyan Chu,Wenxin Hu,Lihua Yang,Shuling Li
Purpose The pathological mechanisms underlying ischemic stroke are highly complex, with the neuroinflammatory response triggered by cerebral ischemia-reperfusion being a major contributor to secondary brain damage. This response significantly impedes neural tissue regeneration. Despite advancements in treatment, current anti-inflammatory strategies remain suboptimal in terms of safety and efficacy. This study aimed to develop an all-natural nanomedicine delivery system for the transnasal administration of puerarin, combined with the endogenous anti-inflammatory peptide Ac2-26, to enhance neuroprotection against ischemic stroke through a synergistic anti-inflammatory approach.Methods In this study, collagen nanoparticles (PueNps) loaded with puerarin were synthesized, followed by the preparation of a chitosan hydrogel. The PueNps and Ac2-26 were co-encapsulated within the hydrogel, resulting in the formation of the PueNps&Ac2-26 gel formulation. The physicochemical properties of this formulation, as well as its biodistribution and anti-ischemic efficacy in the MCAO rat brain, were evaluated.Results In this formulation system, the bioavailability of puerarin and Ac2-26 was enhanced, exhibiting sustained-release properties, which enabled efficient brain-targeted delivery. It effectively alleviated neurological impairment in MCAO rats, reduced the volume of cerebral infarction, and decreased brain water content. Additionally, the PueNps&Ac2-26 gel significantly inhibited neuroinflammation in rats and alleviated oxidative stress.Conclusion The PueNps&Ac2-26 gel is a purely natural and efficient formulation system, offering a promising approach for the clinical treatment of ischemic stroke in the future.
研究领域:
神经科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Jiahao Li,Sharon Shui Yee Leung,Edwin Ho Yin Chan,Cuiping Jiang,Evelyn Tze Yin Ho,Zhong Zuo
Introduction Piperine, the major component in Piper retrofractum and Piper nigrum, had potential therapeutic effects on central nervous system diseases such as Alzheimer’s disease, Parkinson’s disease, epilepsy and fragile X-associated tremor/ataxia syndrome. However, its low aqueous solubility (0.04 mg/mL) limits brain uptake and pharmacological investigations at higher doses. In the current study, formulation strategies and routes of administration were assessed to enhance systemic and brain uptake of piperine.Methods Formulation of piperine nanoparticles (PIP NPs) was developed to enhance its solubility. PIP NPs were prepared using flash nanoprecipitation via a four-stream Multi-Inlet Vortex Mixer, employing an aqueous solution of poloxamer 188 and an ethanolic solution containing piperine and Eudragit L100-55. The process was optimized using the Design of Experiments to minimize the particle size and maximize the encapsulation efficiency of piperine. Additionally, we investigated the impact of administrating PIP NPs via oral and intranasal routes on its systemic and brain uptake.Results The optimized PIP NPs formulation exhibited a particle size of 171.45±2.38 nm, polydispersity index of 0.27±0.01, zeta potential of −43.71±5.11 mV, encapsulation efficiency of 92.49±1.92% and drug loading of 15.07±0.09%. Fourier-transform infrared spectroscopy confirmed the successful encapsulation of piperine into nanoparticles. The PIP NPs could significantly increase the aqueous solubility of piperine from 0.04 mg/mL to 52.31±0.9 mg/mL and release piperine with a 12.83-fold higher rate than that from piperine suspension. Both oral and intranasal administrations of PIP NPs to C57BL/6 mice at 20 mg/kg demonstrated an increase in AUC0-120min for both plasma (7.9–10 times) and brain (4.7–5.0 times) comparing to that from piperine suspension, with no significant difference between these two routes.Discussion Our findings suggested that increasing solubility rather than changing the administration route served as the most critical step to enhance the brain uptake of piperine.
研究领域:
药剂学
·
神经科学
·
药物代谢动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2020
·
IF 2.365
Xinrui Li,Jing Su,Zul Kamal,Pengcheng Guo,Xinyi Wu,Lina Lu,Hongbing Wu,Mingfeng Qiu
Curcumin (Cur) is a promising drug for neurological diseases. Nevertheless, the application of Cur has been limited due to its difficulty in penetrating blood-brain barrier (BBB). Intranasal drug delivery, a noninvasive alternative delivery of Cur, can effectively help Cur cross BBB and inert into central nervous system directly. Odorranalectin (OL) which is the smallest lectin can prolong the residence time of Cur in the nasal mucosa and promote cellular uptake. In this work, a nasal delivery system incorporating OL modified Cur-loaded nanoparticles (Cur–OL–NPs) was developed and expected to bypass BBB and promote the absorption of Cur. We conjugated OL to polyethylene glycol-poly (lactic-co-glycolic acid) (PEG–PLGA), and combined polyethylene glycol-poly (γ-benzyl-L-glutamate) (PEG–PBLG) and OL–PEG–PLGA to prepare nanoparticles to improve the stability, bioavailability and targeting of Cur. Compared with unmodified NPs, increased efficiency of Cur–OL–NPs cellular uptake by Calu-3 cells had been obtained with no severe toxicity. Furthermore, in vivo pharmacokinetic studies also showed that Cur–OL–NPs had higher relative bioavailability. Thus, it is concluded that the results indicated that OL–NPs as carriers of Cur had a promising future in nasal drug delivery system.
研究领域:
药剂学
·
神经科学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Zihe Yang,Linjie Li,Bin Deng,Yusen Xu,Yujing Du,Yongning Lv,Xuejia Zhai
Major depressive disorder is a severe mental condition characterized by abnormalities in the structure and function of the brain. Ketamine is a novel antidepressant that has rapid effects on depression. This drug is clinically used to treat depression in patients with acute suicidal ideation or behavior. It is typically administered at a dose of 84 mg. However, the distribution of ketamine in the body after intranasal administration, particularly in the brain, remains unknown. In the present study, we utilized a high-performance liquid chromatography-tandem mass spectrometry method to measure ketamine concentrations in rat plasma and several tissues. The measurement ranges were 5–8000 ng/mL for the plasma samples and 5–5000 ng/mL for the tissue samples. The pharmacokinetic profile revealed that the rat plasma ketamine concentration rapidly spiked to a peak of 8002 ng/mL within about 5 min, followed by a rapid decline, nearly reaching 0 ng/mL by about 3 h; the half-life was 27 min. Tissue distribution results revealed that ketamine concentrations in different tissues peaked at 5 min. The highest concentration was noted in the kidneys, followed by the liver. In the rat brain regions, ketamine was primarily concentrated in the hypothalamus and hippocampus, with lower concentrations in the striatum and prefrontal cortex. Our novel methodological approach and findings provide a significant theoretical foundation for using ketamine in clinical settings.
研究领域:
药理学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2014
·Vol. 19
·期 4
·4857-4879
·
IF 2.095
Chen Li,Feng Xu,De-Mei Xie,Yu Jing,Ming-Ying Shang,Guang-Xue Liu,Xuan Wang,Shao-Qing Cai
Traditional Chinese Medicine (TCM) nasal therapy has been utilized to treat numerous diseases for over two millennia. It has many advantages compared with other routes. In this article, headspace-solid phase microextraction-gas chromatography-mass spectrometry and high performance liquid chromatography-atmospheric pressure chemical ionization-ion trap-time of flight-multistage mass spectrometry were applied for the first time to analyze the absorbed constituents in rabbit plasma and cerebrospinal fluid (CSF) after intranasal administration of Asari Radix et Rhizoma (AR). In total, 47 absorbed AR constituents including 14 monoterpenes, 10 phenylpropanoids, four benzene derivatives, two alkanes, nineN-alkylamides and eight lignans were tentatively identified in the rabbit plasma and CSF. Thirty-three absorbed constituents are found to have different bioactivities related to the pharmacological actions of AR through bibliography data retrieval. These indicated that many types of constituents of TCM can be absorbed at the nasal cavity into both rabbit blood and CSF. This is the first study to explore the absorption of AR, and comprehensively analyze the absorbed constituents after intranasal administration of TCM. These findings extend our understanding of the effective substances of AR, and inspire us to make a hypothesis on the mechanism of additive effect of multiple constituents of TCMs, which is very worthy of further investigation.Keywords:nasal therapy;Asarum heterotropoidesvar.mandshuricum;intranasal administration;effective substance;cerebrospinal fluid;absorption;SPME;GC-MS;LC-MS;additive effect
研究领域:
中药学
·
分析化学
·
药理学
✓ 已验证
产品关联
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
Asian Journal of Pharmaceutical Sciences
·
2023
·
IF 10.2
Xin Shen,Zhixiang Cui,Yidan Wei,Yingnan Huo,Duo Yu,Xin Zhang,Shirui Mao
The number of people with Alzheimer's disease (AD) is increasing annually, with the nidus mainly concentrated in the cortex and hippocampus. Despite of numerous efforts, effective treatment of AD is still facing great challenges due to the blood brain barrier (BBB) and limited drug distribution in the AD nidus sites. Thus, in this study, using vinpocetine (VIN) as a model drug, the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider, borneol (BOR), using nanoemulsion (NE) as the carrier. First of all, the NE were prepared and characterized. In vivo behavior of the NE after intranasal administration was investigated. Influence of BOR dose, BOR administration route on drug brain targeting behavior was evaluated, and the influence of BOR addition on drug brain subregion distribution was probed. It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery. Compared to intravenous injection, improved brain targeting effect was observed by intranasal route, and drug targeting index (DTI) of the VIN NE group was 154.1%, with the nose-to-brain direct transport percentage (DTP) 35.1%. Especially, remarkably enhanced brain distribution was achieved after BOR addition in the NE, with the extent depending on BOR dose. VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg, with the DTI reaching 596.1% and the DTP increased to 83.1%. BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route. Notably, BOR can remarkably enhance drug distribution in both hippocampus and cortex, the nidus areas of AD. In conclusion, in combination with intranasal delivery and the intrinsic brain guiding effect of BOR, drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly, providing the perquisite for improved therapeutic efficacy of AD.
研究领域:
药理学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Shuang Yu,Dan Li,Ai Shi,Yu Long,Jie Deng,Yin Ma,Xiaoqiu Li,Jing Wen,Yue Hu,Xiaofang He,Yuanyuan Wu,Nan Li,Mengnan Zhao
Baicalin (BA), a multi-target neuroprotective agent, has poor solubility resulting in low bioavailability. In this study, multidrug-loaded liposomes were prepared by encapsulating BA, borneol (BO) and cholic acid (CA) to prevent ischemic stroke. BBC-LP were administered intranasally (i.n.) to deliver into the brain for neuroprotection. Finally, potential mechanism of BBC treating ischemic stroke (IS) was explored by network pharmacology. In this study, BBC-LP was prepared by reverse evaporation method, and the encapsulation efficiency (EE) of the optimized liposomes was 42.69% and the drug loading (DL) was 6.17%. The liposomes had low mean particle size (156.62 ± 2.96 nm), polydispersity index (PDI) (0.195) and zeta potential (−0.99 mv). Compared to BBC, pharmacodynamic studies revealed that BBC-LP significantly improved neurological deficits, brain infarct volume, and cerebral pathology in MCAO rats. Toxicity studies showed that BBC-LP was not irritating to the nasal mucosa. These results suggest that BBC-LP can safely and effectively ameliorate IS injury by i.n. administration. Moreover, it's neuroprotective function may be related to the anti-apoptotic and anti-inflammatory effects exerted by phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway.
研究领域:
药理学
·
神经科学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-26
·
IF 10.6
Hu Yu,Cui Jingwen,Sun Junpeng,Liu Xiaobang,Gao Shuang,Mei Xifan,Wu Chao,Tian He
Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by progressive cognitive and physical impairment. Neuroinflammation is related to AD, and the misfolding and aggregation of amyloid protein in the brain creates an inflammatory microenvironment. Microglia are the predominant contributors to neuroinflammation, and abnormal activation of microglia induces the release of a large amount of inflammatory factors, promotes neuronal apoptosis, and leads to cognitive impairment. In this study, we used microglial membranes containing caffeic acid-coupled carbon quantum dots to prepare a novel biomimetic nanocapsule (CDs-CA-MGs) for the treatment of AD. The application of CDs-CA-MGs via nasal administration can bypass the blood‒brain barrier (BBB) and directly target the site of inflammation. After treatment with CDs-CA-MGs, AD mice showed reduced inflammation in the brain, decreased neuronal apoptosis, and significantly improved learning and memory abilities. In addition, CDs-CA-MGs affect inflammation-related JAK-STAT and Toll-like receptor signaling pathways in AD mice. CDs-CA-MGs significantly downregulated interleukins (IL-1β and IL-6) and tumor necrosis factor (TNF-α). This finding suggested that CDs-CA-MGs may improve cognitive impairment by modulating inflammatory responses. In conclusion, the use of CDs-CA-MGs provides a possible therapeutic strategy for the treatment of AD.Graphical abstract
研究领域:
神经科学
·
药理学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Manli Wang,Yuting Lv,Huipeng Xu,Xiangyu Zhao,Guoqing Zhang,Siwen Wang,Caifen Wang,Wenting Wu,Li Wu,Weifeng Zhu,Jiwen Zhang
The purpose of this study involved the synthesis of supramolecular reservoir (i.e. cyclodextrin metal-organic framework, MOF) using cyclodextrins as building blocks, followed by cross-linking to obtain crosslinked CD framework (CDF) using CD-MOF as template and functionalized with borneol (BO) to enhance rivastigmine (RIV) permeation and facilitate brain targeting via intranasal administration. Utilizing BO modified CDF (BO-CDF) with cubic shape as a carrier for the encapsulation of RIV, a nasal RIV delivery system (RIV@BO-CDF) was fabricated. The particle size of RIV@BO-CDF was approximately 250 nm, and the drug loading capacity reached 15 ± 2 %. BO-CDF improved the mucoadhesion and enhanced RIV permeability with the plasma concentration-time curve (AUC), the brain AUC and the peak drug concentration within brain in rats 1.7, 2.3 and 8 times than that of oral RIV solution, respectively. The relative drug targeting efficiency percentage (DTE, 139.4 %) and direct drug transfer percentage (DTP, 28.3 %) of RIV@BO-COF indicated good targeting efficiency and direct nose-to-brain drug delivery. Overall, this study provides a potential application of supramolecular cyclodextrin-based reservoir to enhance the brain targeting and efficacy of the RIV via nasal delivery.
研究领域:
药剂学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Chenchen Bi,Aiping Wang,Yongchao Chu,Sha Liu,Hongjie Mu,Wanhui Liu,Zimei Wu,Kaoxiang Sun,Youxin Li
Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD.
研究领域:
药剂学
·
神经科学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
VACCINE
·
2014
·
IF 3.485
Qingfeng Liu,Chi Zhang,Xiaoyao Zheng,Xiayan Shao,Xi Zhang,Qizhi Zhang,Xinguo Jiang
The frequent outbreak of respiratory infectious diseases such as influenza and pulmonary tuberculosis calls for new immunization strategies with high effectiveness. Nasal immunization is one of the most potential methods to prevent the diseases infected through the respiratory tract. In this study, we designed a water-soluble system based on antigen/ N -trimethylaminoethylmethacrylate chitosan conjugates for nasal immunization. N -trimethylaminoethylmethacrylate chitosan (TMC) was synthesized by free radical polymerization of chitosan and N -trimethylaminoethylmethacrylate chloride and identified by 1 H NMR and FT-IR. Thiolated ovalbumin (OVA) was covalently conjugated to maleimide modified TMC with high conjugation efficiency. OVA conjugated TMC (OVA–TMC) significantly increased uptake of OVA by Raw 264.7 cells, which was 2.38 times higher than that of OVA/TMC physical mixture (OVA + TMC) at 4 h. After nasal administration, OVA–TMC showed higher transport efficiency to superficial and deep cervical lymph nodes than OVA + TMC or OVA alone. Balb/ C mice were intranasally given with OVA–TMC three times at 2-week internals to evaluate the immunological effect. The serum IgG, IgG1 and IgG2a levels of the OVA–TMC group were 17.9–87.9 times higher than that of the OVA + TMC group and comparable to that of the intramuscular group. The secretory IgA levels in nasal wash and saliva of the OVA–TMC group were 5.2–7.1 times higher than that of the OVA + TMC group while the secretory IgA levels of the intramuscular alum-precipitated OVA group were not increased. After immunofluorescence staining of nasal cavity, IgA antibody secreting cells were mainly observed in the lamina propria regions and glands of nasal mucosa. OVA–TMC showed little toxicity to the nasal epithelia or cilia of rats after nasal administration for three consecutive days. These results demonstrated that antigen conjugated TMC can induce both systemic and mucosal immune responses after nasal administration and may serve as a convenient, safe and effective vaccine for preventing respiratory infectious diseases.
研究领域:
免疫学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）