JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
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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
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神经科学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
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2020
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IF 2.169
Lijun Zhen,Qiuyu Wei,Qilong Wang,Huiyun Zhang,Michael Adu-Frimpong,Caleb Kesse Firempong,Ximing Xu,Jiangnan Yu
6-Gingerol, an active herbal ingredient of ginger has various bioactivities such as anti-neurodegenerative disease, anti-inflammatory and so on. The aim of the present study was to enhance the oral bioavailability and brain distribution of 6-Gingerol via polymeric micelles. A polymeric micelles drug delivery system of 6-Gingerol consisting of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and Poly (ethylene glycol)-poly (ε-caprolactone) (PEG-PCL) was prepared via solvent injection method. The developed 6-Gingerol-loaded TPGS/PEG-PCL micelles (6-GTPMs) were characterized based on particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), drug loading (DL) and in vitro release profile. The pharmacokinetics and tissue distribution studies were also evaluated. The nanoformulation produced a particle size of 73.24 ± 2.84 nm with acceptable PDI (0.129 ± 0.03), zeta potential (−2.74 ± 0.92 mV), DL (4.64%) and EE (79.68%). The in vitro release profile showed that the 6-GTPMs enhanced the solubility of 6-Gingerol, while the pharmaceutical analysis in rats indicated that 6-GTPMs significantly improved the oral bioavailability of 6-Gingerol (about 3 folds) in circulation. The 6-GTPMs exhibited remarkable brain targetability in the tissue distribution analysis. Collectively, a 6-Gingerol polymeric micelle with enhanced oral bioavailability coupled with excellent brain distribution was successfully developed.
研究领域:
药剂学
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生物医学工程
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2021
·Vol. 74
·期 1
·22-31
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IF 3.765
Shen Zhuowei,Hu Haihong,Pan Jie,Xu Mingcheng,Ou Fengting,He Kaifeng,Zeng Kui,Yao Jianbiao,Wang Ruwei,Lou Yan,Zeng Su
Objectives6-Hydroxykynurenic acid (6-HKA) is an organic acid component in extracts of Ginkgo biloba leaves and acts as a major contributor to neurorestorative effects, while its oral bioavailability was low. Therefore, using prodrug method to improve the bioavailability and brain content of 6-HKA is significant.MethodsThree structural modified compounds of 6-HKA were synthesized, and ultra performance liquid chromatography-tandem mass spectrometry methods for quantification of these structural modified compounds in rat plasma and rat brain homogenate were established and comprehensively validated. The methods were effectively applied to investigate the effects of structural modification on apparent permeability coefficients in cells, the pharmacokinetics and the brain distribution in rats.Key findingsThe results illustrated that esterification can greatly improve the apparent permeability coefficient and bioavailability of 6-HKA. Comparing with direct oral administration of 6-HKA, the bioavailability of isopropyl ester was greatly improved (from 3.96 ± 1.45% to 41.8 ± 15.3%), and the contents of 6-HKA in rat brains (49.7 ± 9.2 ng/g brain) were significantly higher after oral administration.ConclusionsThe bioavailability and the brain content of 6-HKA can be improved by the prodrug method. Among three structural modified compounds, isopropyl-esterified 6-HKA was the most promising treatment.
研究领域:
药理学
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神经科学
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药物代谢动力学
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DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
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2013
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IF 1.539
Changhai Qu,Jian Ni,Pei Yang,Hui Zhang,Longfei Lin,Jiang Li,Jingchen Tian,Jing Fu,Xingbin Yin,Hui Kong
Context: Cerebral ischemia–reperfusion (I/R) injury is a secondary injury caused by oxidative stresses and inflammatory responses after recovery from cerebral ischemia. Brain protective drugs were used to reduce the injury. In order to improve the distribution in brain and enhance the brain-protective efficacy, some pharmaceutical technologies were used to achieve brain targeting delivery.Objective: To investigate the physiological disposition of ISA liposome, and provide references for the further study about high-efficacy brain-protective preparations for I/R injury.Materials and methods: Comparative studies were carried out. The pharmacodynamics in t-MCAO model rats were studied first, and then the pharmacokinetics and brain distribution of the two preparations were determined.Results: At the same dose, the efficacy of ISA liposome was better (P < 0.05). The efficacy was dose dependent, with significant difference of 20 mg/kg (P < 0.01) and indistinctive difference of 10 mg/kg (P = 0.22), compared with vehicle-treated rats. The parameters, T1/2β, MRT and AUC were different significantly between the two preparations. The enhancement of brain distribution for ISA in the liposome was obvious, with the maximum concentration 7.18 μg/g, while close to zero for the solution group.Discussion and conclusion: ISA liposome could increase the distribution in brain and enhance the efficacy significantly. The results revealed that the liposomal DDS was potential as a novel strategy for the treatment of cerebral I/R injury. In addition, further targeted modification, such as PEG-modified liposomes, which possess a long circulating property in the bloodstream, would further improve the targeting delivery to the brain and lead to more significant efficacy.
研究领域:
药理学
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神经科学
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药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2018
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IF 5.08
Heran Li,Xueqian Wu,Baixue Yang,Jing Li,Lu Xu,Hongzhuo Liu,Sanming Li,Jinghua Xu,Mingshi Yang,Minjie Wei
Herein, three kinds of mesoporous silica nanoparticles (BMSs) were biomimetically synthesized by using heterocyclic amino acid derivatives as template and their the basic capacity in being drug carriers that covered structure, wettability, degradation, brain uptake, hemocompatibility and toxicity were systematically evaluated. The results indicated that BMSs were kinds of spherical nanoparticles with good biocompatibility. Their in vitro and in vivo behaviors, including degradation, biodistribution and biocompatibility were mainly governed by the wettability which was closely related to the structure and pore diameter of mesoporous silica nanoparticles. BMSs can degrade completely under simulated physiological environments through a time period of 2–13 weeks. They showed the tendency of brain distribution, and the distribution amount peaked at 4 h post administration. Particularly, Trp-BMS (BMS templated by C 16 - l -tryptophan) with the largest amount of OH groups on the surface exhibited highest wettability, fastest degradation rate and the lowest brain distribution ability. Besides, His-BMS (BMS templated by C 16 - l -histidine) and Pro-BMS (BMS templated by C 16 - l -poline) were silica materials with good biocompatibility. Both in vitro and in vivo studies uncovered no significantly toxicity for BMSs and they were proved to be safe when they circulated into the blood. However, Trp-BMS might induce severe hemolysis and cell cycle arrest due to the high wettability. It is believed that appropriate wettability is required for the in vivo application of nanomaterials and the in vivo evaluation of mesoporous silica nanoparticles will provide useful information for understanding the underlining toxicity of biomaterials and bring new insights on designing efficient drug delivery systems.
研究领域:
材料科学
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纳米技术
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药剂学
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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
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