Pharmaceutics
·
2024
·Vol. 16
·期 6
·805
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IF 4.9
Ailing Wu,Houyin Shi,Luhan Yang,Hao Zhang,Xichen Nan,Dan Zhang,Zhuo Zhang,Chun Zhang,Siwei Chen,Xiujuan Fu,Lilan Ou,Lulu Wang,Yanyan Shi,Hao Liu
Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.
研究领域:
药剂学
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神经科学
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临床医学
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产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2020
·
IF 1.902
Qun Ma,Manman Dai,Huimin Zhang,Luyu Bai,Ning He
The effect of different doses of borneol on the pharmacokinetics of vinpocetine after intraocular administration in the rat plasma and the brain was investigated.Intraocular administration of vinpocetine (3 mg/kg) was performed, in combination with different doses (0, 5, 10, and 20 mg/kg) of borneol. Intravenous administration of vinpocetine was used as a control (1 mg/kg). The concentrations of vinpocetine in the rat plasma and the brain were determined using a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method. Using the non-compartmental models with the DSA 2.0 software, the main pharmacokinetics parameters and the brain-targeting effect evaluated.In comparison with intravenous administration, after intraocular administration of vinpocetine alone, the absolute bioavailability (F) of vinpocetine was 43.82% for the plasma, and the drug target index (DTI) was 1.05 for the brain. After intraocular administration of vinpocetine combined with different doses of borneol, the relative bioavailability (Fr) of vinpocetine in the plasma was increased by 130.46–182.90%. The relative bioavailability (Fr) of vinpocetine in the brain was improved (147.19–225.36%). The DTI was 1.12, 1.18, and 1.21 for 5, 10, and 20 mg/kg of borneol, respectively.Compared with the intraocular administration of vinpocetine alone, the co-administration of different doses of borneol resulted in an obvious brain targeting effect.
研究领域:
药理学
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药物代谢动力学
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2019
·
IF 5.808
Caifang Gao,Jianming Liang,Ying Zhu,Chengli Ling,Zhekang Cheng,Ruixiang Li,Jing Qin,Weigen Lu,Jianxin Wang
Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood brain barrier (BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers. Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and glioma-targeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs. The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of menthol-modified casein nanoparticles (M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-M-CA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining of the organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.
研究领域:
药学
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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
CARBOHYDRATE POLYMERS
·
2024
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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
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神经科学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2016
·Vol. 6
·期 37
·31101-31106
·
IF 3.289
Ailing Hui,Shijing Zhu,Huayang Yin,Li Yang,Zheng Zhang,An Zhou,Jian Pan,Wencheng Zhang
A series of ginkgolide B derivatives (GBD) were designed for delivery of ginkgolide B (GB) across the blood–brain barrier to the brain. Three GBD had shown considerable brain-targeting ability in our previous study. Among them, the ginkgolide B pyrazine (PGB) derivative was selected as a promising novel GB derivative because of its highest brain distribution. Further investigations with regard to PGB and GB's effects on inhibiting the expression of P-gp and attenuating the efflux function of P-gp were reported in this study. They were considered a big step towards better understanding the relationship between GBD's brain-targeting behavior and P-gp regulation. Western blot analysis indicated that PGB was more effective in inhibiting the expression of P-gp than GB in rat brain microvessel endothelial cells (rBMECs) and rat cerebral cortexes and hippocampus. Moreover, the efflux function of P-gp via the transportation of rhodamine 123 was significantly inhibited in PGB-treated rat brains. Preventive medication with PGB induced a better protection of the integrity of the BBB in incomplete ischemia mice. Our findings revealed that an attenuated expression level and efflux function of P-gp and improved protective effect could be realized by the ginkgolide B derivative. These investigations will pave the way for designing more efficient brain-targeting derivatives of ginkgolide and some other central nervous system drugs.
研究领域:
药理学
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神经科学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2016
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IF 3.994
Fanfei Meng,Sajid Asghar,Yurui Xu,Jianping Wang,Xin Jin,Zhilin Wang,Jing Wang,Qineng Ping,Jianping Zhou,Yanyu Xiao
Many nanoparticle matrixes have been demonstrated to be efficient in brain targeting, but there are still certain limitations for them. To overcome the shortcomings of the existing nanoparticulate systems for brain-targeted delivery, a lipoprotein resembling protein-free nanostructured lipid carrier (PS80-NLC) loaded with curcumin was constructed and assessed for in vitro and in vivo performance. Firstly, single factor at a time approach was employed to investigate the effects of various formulation factors. Mean particle sizes of ≤100 nm, high entrapment efficiency (EE, about 95%) and drug loading (DL, >3%) were obtained for the optimized formulations. In vitro release studies in the presence of plasma indicated stability of the formulation under physiological condition. Compared with NLC, PS80-NLC showed noticeably higher affinity for bEnd.3 cells (1.56 folds greater than NLC) but with lower uptake in macrophages. The brain coronal sections showed strong and widely distributed fluorescence intensity of PS80-NLC than that of NLC in the cortex. Ex vivo imaging studies further confirmed that PS80-NLC could effectively permeate BBB and preferentially accumulate in the brain (2.38 times greater than NLC). The considerable in vitro and in vivo performance of the safe and biocompatible PS80–NLC makes it a suitable option for further investigations in brain targeted drug delivery .
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
JOURNAL OF DRUG TARGETING
·
2025
·
IF 3.9
Jing Jiang,Yue Xing,Shumeng Liu,Yue Na,Xia Lei,Fang Geng,Yafeng Zhang,Lihong Yang,Ning Zhang
Naringin (4',5,7-trihydroxyflavanone-7-rhamnoglucoside, NG), a potential treatment for Alzheimer’s disease (AD), has strong neuroprotective effects but is limited by poor solubility, low bioavailability, and limited brain accumulation. To address these issues, we developed ANG-NG-NPs, a novel NG-loaded poly (ethylene glycol)-poly(ε-caprolactone) copolymers (PEG-PCL) nanoparticle modified with the brain-targeting peptide Angiopep-2 (TFFYGGSRGKRNNFKTEEY, ANG). ANG-NG-NPs exhibited an average size of 126.1 ± 4.50 nm, a zeta potential of -2.97 ± 0.29 mV, 73.43% ± 0.80% encapsulation efficiency (EE), and 24.68% ± 0.45% drug loading capacity (LC). In vitro release studies confirmed its sustained-release properties. In vivo, ANG-NG-NPs extended NG’s circulation time and increased brain uptake. Notably, ANG-NG-NPs restored learning and memory in APP/PS1 mice, improved hippocampal cell health, and reduced hyperphosphorylated tau protein (p-Tau) expression. These findings suggest ANG-NG-NPs as a promising brain-targeting system for treating central nervous system disorders.
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
SAUDI PHARMACEUTICAL JOURNAL
·
2022
·
IF 4.562
Ge Ou,Qian Li,Lin Zhu,Yuanyuan Zhang,Yijing Liu,Xin Li,Lina Du,Yiguang Jin
Armodafinil inclusion complex (AIC) hydrogel was prepared and evaluated for its therapeutic effect on Post-traumatic Stress Disorder (PTSD). After computer simulation and physicochemical property investigation, the AIC was formed by lyophilization of armodafinil with ethanol as solvent and hydroxypropyl-beta-cyclodextrin (HP-β-CD) aqueous solution, in which the molar ratio of armodafinil and HP-β-CD was 1–1. The AIC encapsulation efficiency (EE) was (90.98 ± 3.72)% and loading efficiency (LE) was (13.95 ± 0.47)% and it increased the solubility of armodafinil in aqueous solution to 21 times. AIC hydrogel was prepared by adding AIC to methylcellulose (MC) hydrogels (3.33% w/v), and its higher drug release amount and slower release rate were testified by the in-vitro release assay and the rheological test. The mucosa irritation of AIC hydrogel was also evaluated. Healthy group, Model group, Sertraline group with 30 mg/kg sertraline gavage, AIC Hydrogel group with 20 mg/kg AIC hydrogel intranasal administration and AIC Aqueous Solution group with 20 mg/kg AIC aqueous solution gavage were set up for the treatment of mice with PTSD generated from foot shock method. Based on freezing response test in fear-conditioning box and open field test, compared with other groups, PTSD mice in AIC Hydrogel group showed significant improvement in behavioral parameters after 11 days of continuous drug administration and 5 days of drug withdrawal. After sacrifice, the plasma CORT level of PTSD mice in AIC Hydrogel group was elevated compared to Model group. Besides, the western blot (WB) of hippocampal brain-derived neurotrophic factor (BDNF) and amygdala dopamine transporter (DAT) immunohistochemistry sections indicated that AIC hydrogel had a protective effect on the brain tissue of PTSD mice. The brain targeting of intranasal administration was evaluated by fluorescence imaging characteristics of Cy7 hydrogel in the nasal route of drug administration, pharmacokinetics and in-vivo distribution of armodafinil. In short, AIC hydrogel is a promising formulation for the treatment of PTSD based on its high brain delivery and anti-PTSD effect.
研究领域:
药剂学
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神经科学
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精神医学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Hui Song,Man Wei,Nan Zhang,He Li,Xiaochuan Tan,Yujia Zhang,Wensheng Zheng
Introduction The incidence of central nervous system disease has increased in recent years. However, the transportation of drug is restricted by the blood–brain barrier, contributing to the poor therapeutic effect in the brain. Therefore, the development of a new brain-targeting drug delivery system has become the hotspot of pharmacy.Materials and methods Borneol, a simple bicyclic monoterpene extracted from Dryobalanops aromatica, can direct drugs to the upper body parts according to the theory of traditional Chinese medicine. Dioleoyl phosphoethanolamine (DOPE) was chemically modified by borneol as one of the lipid materials of solid lipid nanoparticle (SLN) in the present study.Results The borneol-modified chemically solid lipid nanoparticle (BO-SLN/CM), borneol-modified physically solid lipid nanoparticle (BO-SLN/PM), and SLN have similar diameter (of about 87 nm) and morphological characteristics. However, BO-SLN/CM has a lower cytotoxicity, higher cell uptake, and better blood–brain barrier permeability compared with BO-SLN/PM and SLN. BO-SLN/CM has a remarkable targeting function to the brain, while BO-SLN/ PM and SLNs are concentrated at the lung.Conclusion The present study provides an excellent drug delivery carrier, BO-SLN/CM, having the application potential of targeting to the brain and permeating to the blood–brain barrier.
研究领域:
药学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yan Song,Luyao Wang,Tingting Peng,Lingling Shan,Bo Wan,Mingtan Tang,Yuxia Luan,Yue Jiang,Wenxiu He
Dysfunction of the neurovascular unit significantly impacts the prognostic outcomes of ischemic stroke. However, effective strategies to comprehensively modulate the neurovascular unit have yet to be developed. In this work, we introduce a brain-targeting biomimetic nanozyme, A@HPB@THSA, designed to mitigate neurovascular unit dysfunction following ischemia/reperfusion. Specifically, aspirin is encapsulated within hollow Prussian blue nanozyme, which is subsequently modified with brain-targeting T7 peptide-conjugated human serum albumin, ultimately forming the composite A@HPB@THSA. The overexpression of transferrin receptors on cerebral vascular endothelial cells, along with compromised blood-brain barrier (BBB) permeability, facilitates the accumulation of A@HPB@THSA at cerebral ischemic lesions. The hollow Prussian blue nanozyme component effectively scavenges reactive oxygen species in ischemia/reperfusion-affected brain cells. While the aspirin component inhibits platelets aggregation and neutrophils infiltration, thereby preventing microvascular “no-reflow” and preserving the integrity of the BBB. In rat models of transient middle cerebral artery occlusion, A@HPB@THSA demonstrated comprehensive modulation of the neurovascular unit, including reduced BBB permeability, promotion of microglia polarization toward an anti-inflammatory phenotype, and enhanced neuronal survival. This work provides a promising platform to reverse dysfunctional neurovascular unit for ischemic stroke treatment.
研究领域:
医学
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神经科学
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药剂学
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产品关联
DOI
PubMed
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
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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
MATERIALS TECHNOLOGY
·
2024
·
IF 2.9
Xin Tian,Taoxiang Shi,Shiyang Fu,Zheda Liu,Yalan You,Keke Chen,Anqi Yao,Chengguang Zhu,Minhui Zeng,Wenfang Tang,Xiaojun Tao,Xiangling He
In this study, we grafted cholesterol with pullulan to synthesize hydrophobic pullulan(CHP). Three CHP polymers (CHP1, CHP2, and CHP3), with different degrees of substitution were designed by changing the feed ratio of cholesterol to pullulan. The 1H-NMR results showed that the hydrophobic substitutability of CHP1, CHP2, and CHP3 were calculated to be 8.26%, 5.67%, and 3.52%, respectively. The sizes of CHP1 NPs, CHP2 NPs, and CHP3 NPs were (118±7.9), (123±4.7) and (158±9.3) nm, respectively. The CHP NPs embedded with VCR and adsorbed Tween 80 (CHPT@VCR NPs). The results of microscale thermal imaging (MST) testing indicated the CHP-1 NPs with the highest degree of cholesterol substitution possessed the highest adsorption capacity for Tween 80. In vitro pharmacological studies were conducted in SJ-GBM2 cells, the results showed that the tumor cells inhibition rate and the cellular uptake rate of CHPT@VCR-1 NPs were the highest compared with CHPT@VCR-2 NPs and CHPT@VCR-3 NPs.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
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