eLife
·
2023
·
IF 7.7
Yang He,Taohui Liu,Quansheng He,Wei Ke,Xiaoyu Li,Jinjin Du,Suixin Deng,Zhenfeng Shu,Jialin Wu,Baozhi Yang,Yuqing Wang,Ying Mao,Yanxia Rao,Yousheng Shu,Bo Peng
General anesthesia leads to a loss of consciousness and an unrousable state in patients. Although general anesthetics are widely used in clinical practice, their underlying mechanisms remain elusive. The potential involvement of nonneuronal cells is unknown. Microglia are important immune cells in the central nervous system (CNS) that play critical roles in CNS function and dysfunction. We unintentionally observed delayed anesthesia induction and early anesthesia emergence in microglia-depleted mice. We found that microglial depletion differentially regulates neuronal activities by suppressing the neuronal network of anesthesia-activated brain regions and activating emergence-activated brain regions. Thus, microglia facilitate and stabilize the anesthesia status. This influence is not mediated by dendritic spine plasticity. Instead, it relies on the activation of microglial P2Y12 and subsequent calcium influx, which facilitates the general anesthesia response. Together, we elucidate the regulatory role of microglia in general anesthesia, extending our knowledge of how nonneuronal cells modulate neuronal activities.
研究领域:
神经科学
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麻醉学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2024
·
IF 11.4
Xuequan Liu,Xuequan Sun,Hongyu Zhu,Rubing Yan,Chang Xu,Fangxing Zhu,Ruijie Xu,Jing Xia,He Dong,Bingcheng Yi,Qihui Zhou
Introduction One of the methods for pain management involves the use of local anesthesia, which numbs sensations in specific body regions while maintaining consciousness. Objectives Considering the certain limitations (e.g., pain, the requirement of skilled professionals, or slow passive diffusion) of conventional delivery methods of local anesthetics, developing alternative strategies that offer minimally invasive yet therapeutically effective delivery systems is of great concern for ophthalmic regional anesthesia. Methods and results In this study, a rapidly dissolving cambered microneedle (MNs) patch, composed of poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA) and served as a delivery system for lidocaine (Lido) in local anesthesia, was developed taking inspiration from the mosquito proboscis’s ability to extract blood unnoticed. The lidocaine-containing MNs patch (MNs@Lido) consisted of 25 microneedles with a four-pronged cone structure (height: 500 μm, base width: 275 μm), arranged in a concentric circle pattern on the patch, and displays excellent dissolubility for effective drug delivery of Lido. After confirming good cytocompatibility, MNs@Lido was found to possess adequate rigidity to penetrate the cornea without causing any subsequent injury, and the created corneal pinhole channels completely self-healed within 24 h. Interestingly, MNs@Lido exhibited effective analgesic effects for local anesthesia on both heel skin and eyeball, with the sustained anesthetic effect lasting for at least 30 min. Conclusions These findings indicate that the mosquito proboscis-inspired cambered MNs patch provides rapid and painless local anesthesia, overcoming the limitations of conventional delivery methods of local anesthetics, thus opening up new possibilities in the treatment of ophthalmic diseases.
研究领域:
药学
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生物医学工程
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眼科学
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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
Food Analytical Methods
·
2023
·Vol. 16
·期 3
·633-649
·
IF 2.9
Li Fan,Wang Zhanhua,Zhu Bingqi,Xu Xiaoying,Liu Zhu
Anesthetics are widely applied in cultivation and transportation of aquatic products to reduce the metabolism of fish and avoid some stress reactions. The overdose of using anesthetics or the occurrence of their residues in the aquatic products may negatively affect human health after consumption. A rapid screening procedure and a new analytical method for the simultaneous determination of 14 anesthetics was established in this study. The compounds were extracted from fish and shrimp matrices by sodium acetate buffer solution, cleaned up via solid-phase extraction, and then were analyzed using an ultrahigh-performance liquid chromatography system coupled with a tandem quadrupole-time-of-flight mass spectrometer (UPLC-Q-TOF–MS) in a positive-ion mode. Methodological verification analyses, including linearity, precision, recovery, limit of detection (LOD), and limit of quantification (LOQ), were conducted to validate the method. The correlation coefficient of the calibration curves of each anesthetic exceeded 0.99. The average recoveries of this analysis method varied from 72.36 to 111.27% with relative standard deviations less than 5%. The detection limit of anesthetics reached 0.3–0.7 μg/kg. Agilent Mass Hunter Personal Compound Database Library (PCDL) Manager was used to establish a database of 14 anesthetics and 8 isotope internal standards, which enabled a quick screening and analysis without standard substances. The results of the spiked blank samples demonstrated reliability of the screening method with mass deviations less than 5 ppm and the scores determined by relative molecular mass, retention time, isotope ratio, and distribution all greater than 85. In addition, according to the fragmentation information of mass spectrometry, the fragmentation rules of some anesthetics were summarized. This method was validated with reliable results in quantitative and qualitative analysis and could be used as regulatory measures for anesthetics in aquatic products.
研究领域:
食品安全
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分析化学
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环境科学
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产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
·
IF 4.5
Yanan Mao,Rui Yao,Xiufeng Zhang,Chao Zhong,Khaydar E. Yunusov,Zhong Shen,Jianwei Pan,Guohua Jiang
Pain is a subjective sensation associated with actual or potential tissue damage, presenting a global clinical challenge that not only significantly impacts individuals' quality of life, but also incurs substantial economic burdens. In this study, polymer microneedles (MNs) with hollow double-layer shell structure had been designed for local long-lasting analgesia. The hollow and inner-shell layer were formed by a microtemplate method under vacuum and UV cross-linking. The formed cavities in MNs could be utilized for loading lidocaine hydrochloride (LidH) powder to increase the drug loading capacity. The outer-shell layer formed a frozen dip-coating process was composed of poly(vinylpyrrolidone) (PVP), citric acid (CA), sodium bicarbonate (NaHCO 3 ), and small amount of LidH. After insertion into skin, the outermost shell of MNs could been rapidly dissolved, leading to a rapid release of LidH to achieve a rapid analgesia. Subsequently, the LidH loaded within the cavity could be continuously released due to swelling of the inner shell, thereby to obtain long-term analgesic effect. In vivo local analgesic tests reveled that local analgesic time could be extended up to 48 h, showing a potential possibility to reduce administration frequency and improve patient comfort.
研究领域:
药剂学
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生物医学工程
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产品关联
DOI
高影响因子
Biomedicines
·
2021
·Vol. 9
·期 6
·592
·
IF 6.081
Yang Liu,Maosen Cheng,Junqi Zhao,Xiaoying Zhang,Zhen Huang,Yuhui Zang,Ying Ding,Junfeng Zhang,Zhi Ding
This study aimed to improve the transdermal delivery of lidocaine hydrochloride (LidH) using elastic nano-liposomes (ENLs) and microneedle (MN) array pretreatment. LidH-containing ENLs were prepared using soybean phosphatidylcholine and cholesterol, with Span 80 or Tween 80, using a reverse-phase evaporation method. The ENL particle size, stability, and encapsulation efficiency (EE) were characterized and optimized based on the component ratio, pH, and type of surfactant used. In vitro transdermal diffusion study was performed on MN-pretreated mouse skin using Franz diffusion cells. The anesthetic effects of LidH in various formulations after dermal application were evaluated in vivo in rats by measuring the tail withdrawal latency after photothermic stimulation. Stable LidH-loaded Tween 80 or Span 80 ENLs were obtained with particle sizes of 115.8 and 146.6 nm and EEs of 27% and 20%, respectively. The formulations did not exert any cytotoxicity in HaCaT cells. Tween 80 and Span 80 ENL formulations showed enhanced LidH delivery on pretreated mice skin in vitro and prolonged the anesthetic effect in vivo compared to that by LidH application alone. LidH-loaded ENLs applied to MN-pretreated skin can shorten the onset time and prolong the anesthetic effect safely, which merits their further optimization and practical application.Keywords:lidocaine;solid microneedles;elastic vesicles;topical drug administration;anesthesia
研究领域:
药剂学
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生物医学工程
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皮肤科学
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DOI
PubMed
高影响因子
AQUACULTURE RESEARCH
·
2019
·Vol. 50
·期 11
·3138-3153
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IF 1.502
Xiaohuan Cao,Yajun Wang,Na Yu,Qijun Le,Jiabao Hu,Yang Yang,Siwen Kuang,Man Zhang,Yibo Sun,Weiwei Gu,Xiaojun Yan
Anaesthetics are widely used in aquaculture as a method of stress relief. However, few studies have reported the influence of anaesthetics on the immune system of fish. Therefore, in the present study, we selected two different anaesthetics, MS-222 (100 mg/L) and eugenol (20 mg/L), to anaesthetize crucian carp and analyse the transcriptome. It was found that over 137 million high-quality reads were generated and de novo assembled into a final set of 97,556 unigenes. A total of eight differentially expressed genes (DEGs) related to the immune response were co-expressed in the two anaesthetic groups. GO and the KEGG revealed that these genes functioned primarily to enrich antigen processing and presentation pathways, including MHCI , MHCIα , p-MHCIIα , P-MHCIIα , CD74 , MHCII antigen and MHCII antigenα . Moreover, LRRFIP2 was found be associated with the immune response. Consistent with the transcriptome findings, qPCR verified the changes in the relative level of expression of these genes. Furthermore, long-term exposure to low concentrations of MS-222 (30 mg/L) and eugenol (8 mg/L) showed an impact on these immune genes. In conclusion, anaesthetics used in high or low concentrations for treatment and transport could affect the immune system in fish species. While eugenol was associated with an earlier activation of immune gene expression, MS-222 exhibited more significant effects on the immune response. These findings improve the understanding of the mechanisms of anaesthetics on immune damage and will be of great value for future studies involving anaesthetic selection and treatment for fish.
研究领域:
水产养殖学
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免疫学
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分子生物学
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产品关联
DOI
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 6
·805
·
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
MOLECULES
·
2022
·Vol. 27
·期 17
·5509
·
IF 4.927
Shan-Yan Liang,Fang Shi,Yong-Gang Zhao,Hong-Wei Wang
In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl–carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic solid-phase extraction (MSPE) for the preconcentration of seven local anesthetic drugs (procaine, lidocaine, mepivacaine, oxybuprocaine, bupivacaine, tetracaine, and cinchocaine) from human plasma. The separation and determination of analytes were performed on high-performance liquid chromatography with UV detection. Several factors affected the extraction efficiency, such as the amount of adsorbents used, extraction time, sample pH, and optimization of elution conditions. Under optimal conditions, satisfactory linear relationships were obtained in the range of 0.02–5.00 mg/L, with the limits of detection (LOD) ranging from 0.003 mg/L to 0.008 mg/L. The recoveries of analytes for spiked human plasma were in the range of 82.0–108%. Moreover, the precision with intra-day and inter-day RSD values were obtained in the range of 1.5–7.7% and 1.5–8.3%. The results indicated that this method could determine the concentration of seven local anesthetic drugs in human plasma with high precision and repeatability and provide support for the clinical monitoring of the concentration of local anesthetic drugs in human plasma.Keywords:HPLC;MSPE;local anesthetic drugs;human plasma
研究领域:
分析化学
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医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2018
·
IF 2.297
Hao Liu,Xuemei Zhou,Yingying Wang,Menglu Yang,Xiaohui Xu,Ailing Wu
Etomidate is one of the first-line general anesthetic agents , with distinguished properties such as rapid onset, excellent cardiovascular stability, minimal impact on respiratory system, etc . However, the clinical application of etomidate preparation is often confined by the notable defects of both the drug and its current formulations. Previously, we reported a new etomidate formulation based on Pluronic F108 micelle which demonstrated improved anesthetic effects. Nevertheless, the micellar encapsulation of etomidate was limited using only one kind of Pluronic, which required organic solvents to modulate the hydrophobicity . Besides, the biocompatibility of this formulation was not yet clear. Herein, we reported that mixed nanomicelles consisting of different Pluronic could make full advantage of each loading material, which led to improved physicochemical properties for the delivery of etomidate. Moreover, in vivo studies demonstrated that, the etomidate-loaded mixed micelle (Eto-PFM) maintained the anesthetic effects and rapid onset property of etomidate, with a broad safe dose range. The potential mechanisms of the acute toxicity were also discussed. The results suggest that Eto-PFM is a promising etomidate preparation with the potential to further develop as an alternative to the current etomidate preparations.
研究领域:
药剂学
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生物医学工程
·
毒理学
✓ 已验证
DOI
高影响因子
Analytical Methods
·
2023
·Vol. 15
·期 33
·4179-4186
·
IF 3.1
Xiaoxiao Li,Pan Chang,Xing Liu,Zhongjun Zhao,Wenwen Li,Yi Kang,Yixiang Duan,Wensheng Zhang
Ciprofol (HSK 3486, C14H20O), a novel 2,6-disubstituted phenol derivative similar to propofol, is a new type of intravenous general anaesthetic. We found that the exhaled ciprofol concentration could be measured online by ultraviolet time-of-flight mass spectrometry (UV-TOFMS), which could be used to predict the plasma concentration and anaesthetic effects of ciprofol. In this study, we present the calibration method and validation results of UV-TOFMS for the quantification of ciprofol gas. Using a self-developed gas generator to prepare different concentrations of ciprofol calibration gas, we found a linear correlation between the concentration and intensity of ciprofol from 0 parts per trillion by level (pptv) to 485.85 pptv (R2 = 0.9987). The limit of quantification was 48.59 pptv and the limit of detection was 7.83 pptv. The imprecision was 12.44% at 97.17 pptv and was 8.96% at 485.85 pptv. The carry-over duration was 120 seconds. In addition, we performed a continuous infusion of ciprofol in beagles, measured the exhaled concentration of ciprofol by UV-TOFMS, determined the plasma concentration by high-performance liquid chromatography, and monitored the anaesthetic effects as reflected by the bispectral index value. The results showed that the exhaled and plasma concentrations of ciprofol were linearly correlated. The exhaled ciprofol concentration correlated well with the anaesthetic effect. The study showed that we could use UV-TOFMS to provide a continuous measurement of gaseous ciprofol concentration at 20 second intervals.
研究领域:
药理学
·
分析化学
·
麻醉学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL MICRODEVICES
·
2024
·Vol. 26
·期 1
·1-12
·
IF 3
Mao Yanan,Zhang Xiufeng,Sun Yanfang,Shen Zhong,Zhong Chao,Nie Lei,Shavandi Amin,Yunusov Khaydar E.,Jiang Guohua
There is an urgent need for research into effective interventions for pain management to improve patients’ life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs’ tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.
研究领域:
药剂学
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生物医学工程
·
疼痛管理
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHYSICAL CHEMISTRY B
·
2024
·
IF 2.8
Yiqi Bai,Huimin Xu,Haoyu Wang,Yixiao Fan,Xiaohong Li,Yunchao Li,Louzhen Fan,Yang Zhang,Ling Qi,Yong Li
Safe and efficient local anesthetic delivery carriers are crucial for long-term anesthesia and analgesics in clinical treatment. But currently, most of the local anesthetic carriers still have some disadvantages such as low drug-loading capacity, drug leakage, and potential side effects. Here, we report red-emissive carbon dots (Cys-CDs) synthesized by choosing cysteine and citric acid as precursors, which contain a large and intact sp2-domain with rich hydrophilic groups around the edge. The special structure of Cys-CDs is conducive to the efficient loading of procaine (PrC) via strong π–π stacking interactions. Based on the strong noncovalent interactions between them, the PrC loaded on Cys-CDs achieved slow release in vitro and had a long-lasting nerve blocking effect in vivo, which is 4-fold more than that of free PrC. More importantly, PrC/Cys-CDs do not cause any toxicity and inflammation during treatment owing to slow release of PrC and good water solubility of Cys-CDs, thus demonstrating the potential clinical application of CDs in long-lasting analgesia.
研究领域:
药学
·
材料科学
·
生物医学工程
✓ 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）