scholarly journals Pharmacokinetic properties of the temozolomide perillyl alcohol conjugate (NEO212) in mice

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Hee-Yeon Cho ◽  
Steve Swenson ◽  
Thu Zan Thein ◽  
Weijun Wang ◽  
Neloni R Wijeratne ◽  
...  
Keyword(s):  
High Performance ◽  
Perillyl Alcohol ◽  
Normal Brain ◽  
Oral Gavage ◽  
Preclinical Development ◽  
Primary Metabolites ◽  
Mouse Plasma ◽  
Pharmacokinetic Properties ◽  
Natural Monoterpene ◽  
Further Development

Abstract Background NEO212 is a novel small-molecule anticancer agent that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH) to the alkylating agent temozolomide (TMZ). It is undergoing preclinical development as a therapeutic for brain-localized malignancies. The aim of this study was to characterize metabolism and pharmacokinetic (PK) properties of NEO212 in preclinical models. Methods We used mass spectrometry (MS) and modified high-performance liquid chromatography to identify and quantitate NEO212 and its metabolites in cultured glioblastoma cells, in mouse plasma, brain, and excreta after oral gavage. Results Our methods allowed identification and quantitation of NEO212, POH, TMZ, as well as primary metabolites 5-aminoimidazole-4-carboxamide (AIC) and perillic acid (PA). Intracellular concentrations of TMZ were greater after treatment of U251TR cells with NEO212 than after treatment with TMZ. The half-life of NEO212 in mouse plasma was 94 min. In mice harboring syngeneic GL261 brain tumors, the amount of NEO212 was greater in the tumor-bearing hemisphere than in the contralateral normal hemisphere. The brain:plasma ratio of NEO212 was greater than that of TMZ. Excretion of unaltered NEO212 was through feces, whereas its AIC metabolite was excreted via urine. Conclusions NEO212 preferentially concentrates in brain tumor tissue over normal brain tissue, and compared to TMZ has a higher brain:plasma ratio, altogether revealing favorable features to encourage its further development as a brain-targeted therapeutic. Its breakdown into well-characterized, long-lived metabolites, in particular AIC and PA, will provide useful equivalents for PK studies during further drug development and clinical trials with NEO212.

scholarly journals Intranasal administration of the chemotherapeutic perillyl alcohol results in selective delivery to the cerebrospinal fluid in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Geetika Nehra ◽  
Shannon Andrews ◽  
Joan Rettig ◽  
Michael N. Gould ◽  
Jill D. Haag ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Tumors ◽  
Nasal Mucosa ◽  
Brain Cancer ◽  
Intranasal Administration ◽  
High Performance ◽  
Early Stage ◽  
Plasma Concentrations ◽  
Perillyl Alcohol ◽  
Systemic Absorption

AbstractPerillyl alcohol (POH) has been extensively studied for the treatment of peripheral and primary brain tumors. The intranasal route of administration has been preferred for dosing POH in early-stage clinical trials associated with promising outcomes in primary brain cancer. However, it is unclear how intranasal POH targets brain tumors in these patients. Multiple studies indicate that intranasally applied large molecules may enter the brain and cerebrospinal fluid (CSF) through direct olfactory and trigeminal nerve-associated pathways originating in the nasal mucosa that bypass the blood–brain barrier. It is unknown whether POH, a small molecule subject to extensive nasal metabolism and systemic absorption, may also undergo direct transport to brain or CSF from the nasal mucosa. Here, we compared CSF and plasma concentrations of POH and its metabolite, perillic acid (PA), following intranasal or intravascular POH application. Samples were collected over 70 min and assayed by high-performance liquid chromatography. Intranasal administration resulted in tenfold higher CSF-to-plasma ratios for POH and tenfold higher CSF levels for PA compared to equal dose intravascular administration. Our preclinical results demonstrate POH undergoes direct transport from the nasal mucosa to the CSF, a finding with potential significance for its efficacy as an intranasal chemotherapeutic for brain cancer.

scholarly journals Simultaneously Regulating Uniform Zn2+ Flux and Electron Conduction by MOF/rGO Interlayers for High-Performance Zn Anodes

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ziqi Wang ◽  
Liubing Dong ◽  
Weiyuan Huang ◽  
Hao Jia ◽  
Qinghe Zhao ◽  
...  
Keyword(s):  
High Performance ◽  
Surface Passivation ◽  
Coulombic Efficiency ◽  
Low Cost ◽  
Metal Organic Framework ◽  
Growth Surface ◽  
Electron Conduction ◽  
Reduced Graphene ◽  
Metal Organic ◽  
Further Development

AbstractOwing to the merits of low cost, high safety and environmental benignity, rechargeable aqueous Zn-based batteries (ZBs) have gained tremendous attention in recent years. Nevertheless, the poor reversibility of Zn anodes that originates from dendrite growth, surface passivation and corrosion, severely hinders the further development of ZBs. To tackle these issues, here we report a Janus separator based on a Zn-ion conductive metal–organic framework (MOF) and reduced graphene oxide (rGO), which is able to regulate uniform Zn2+ flux and electron conduction simultaneously during battery operation. Facilitated by the MOF/rGO bifunctional interlayers, the Zn anodes demonstrate stable plating/stripping behavior (over 500 h at 1 mA cm−2), high Coulombic efficiency (99.2% at 2 mA cm−2 after 100 cycles) and reduced redox barrier. Moreover, it is also found that the Zn corrosion can be effectively retarded through diminishing the potential discrepancy on Zn surface. Such a separator engineering also saliently promotes the overall performance of Zn|MnO2 full cells, which deliver nearly 100% capacity retention after 2000 cycles at 4 A g−1 and high power density over 10 kW kg−1. This work provides a feasible route to the high-performance Zn anodes for ZBs.

scholarly journals Nonvolatile Ternary Resistive Memory Performance of a Benzothiadiazole-Based Donor–Acceptor Material on ITO-Coated Glass

Coatings ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 318
Author(s):  
Yang Li ◽  
Cheng Zhang ◽  
Zhiming Shi ◽  
Jingni Li ◽  
Qingyun Qian ◽  
...  
Keyword(s):  
Data Storage ◽  
High Performance ◽  
Memory Performance ◽  
Resistive Memory ◽  
Molecular Systems ◽  
Threshold Voltages ◽  
Donor Acceptor ◽  
Low Threshold ◽  
Multilevel Memory ◽  
Further Development

The explosive growth of data and information has increasingly motivated scientific and technological endeavors toward ultra-high-density data storage (UHDDS) applications. Herein, a donor−acceptor (D–A) type small conjugated molecule containing benzothiadiazole (BT) is prepared (NIBTCN), which demonstrates multilevel resistive memory behavior and holds considerable promise for implementing the target of UHDDS. The as-prepared device presents distinct current ratios of 105.2/103.2/1, low threshold voltages of −1.90 V and −3.85 V, and satisfactory reproducibility beyond 60%, which suggests reliable device performance. This work represents a favorable step toward further development of highly-efficient D−A molecular systems, which opens more opportunities for achieving high performance multilevel memory materials and devices.

scholarly journals Preclinical Pharmacokinetics of Scoparone, Geniposide and Rhein in an Herbal Medicine Using a Validated LC-MS/MS Method

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2716 ◽  
Author(s):  
Tun-Pin Hsueh ◽  
Tung-Hu Tsai
Keyword(s):  
Bioactive Compounds ◽  
Pharmacokinetic Study ◽  
High Performance ◽  
Low Dose ◽  
Rat Plasma ◽  
Herbal Formula ◽  
Preclinical Pharmacokinetics ◽  
Pharmacokinetic Properties ◽  
Liquid Chromatography Tandem Mass

The herbal formula Yin-Chen-Hao-Tang has been reported to have anti-fibrosis properties. The aim of this study was to reveal the pharmacokinetic characteristics of bioactive compounds in this herbal formula. A new high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of scoparone, geniposide and rhein in rat plasma. A pharmaceutical herbal powder was administered to rats at doses of 1 g/kg and 3 g/kg orally. The method showed excellent linearity (r2 > 0.999) and validation was successfully conducted for the pharmacokinetic study. The results show that the Cmax values and areas under the curve of scoparone, geniposide and rhein were higher and not proportional to the dose in rat plasma, while the Tmax and half-life values were consistent in the group that received 1 g/kg. The clearance of the higher dose (3 g/kg) did not decrease proportionally to that of the low dose. The results showed the nonlinear pharmacokinetic properties of scoparone, geniposide and rhein in Yin-Chen-Hao-Tang that suggested possible accumulation of bioactive compounds through oral administration. This pharmacokinetic study reveals that an increased dose of this herbal formula would largely increase the maximum concentration and bioavailability of scoparone, geniposide and rhein.

Liquid chromatography–tandem mass spectrometric assay for diclofenac and three primary metabolites in mouse plasma

2008 ◽  
Vol 872 (1-2) ◽  
pp. 77-82 ◽  
Author(s):  
Rolf W. Sparidans ◽  
Jurjen S. Lagas ◽  
Afred H. Schinkel ◽  
Jan H.M. Schellens ◽  
Jos H. Beijnen
Keyword(s):  
Liquid Chromatography ◽  
Mass Spectrometric ◽  
Tandem Mass ◽  
Primary Metabolites ◽  
Mouse Plasma ◽  
Liquid Chromatography Tandem Mass ◽  
Tandem Mass Spectrometric

scholarly journals Single-Dose Pharmacokinetics of Meropenem during Continuous Venovenous Hemofiltration

1998 ◽  
Vol 42 (9) ◽  
pp. 2417-2420 ◽  
Author(s):  
Florian Thalhammer ◽  
Peter Schenk ◽  
Heinz Burgmann ◽  
Ibrahim El Menyawi ◽  
Ursula M. Hollenstein ◽  
...  
Keyword(s):  
High Performance ◽  
Peak Plasma ◽  
Continuous Venovenous Hemofiltration ◽  
Drug Concentrations ◽  
Elimination Half ◽  
Pharmacokinetic Properties ◽  
Severe Infections ◽  
Total Body ◽  
Trough Levels ◽  
Body Clearance

ABSTRACT The pharmacokinetic properties of meropenem were investigated in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH). All patients received one dose of 1 g of meropenem intravenously. High-flux polysulfone membranes were used as dialyzers. Meropenem levels were measured in plasma and ultrafiltrate by high-performance liquid chromatography. The total body clearance and elimination half-life were 143.7 ± 18.6 ml/min and 2.46 ± 0.41 h, respectively. The post- to prehemofiltration ratio of meropenem was 0.24 ± 0.06. Peak plasma drug concentrations measured 60 min postinfusion were 28.1 ± 2.7 μg/ml, and trough levels after 6 h of CVVH were 6.6 ± 1.5 μg/ml. The calculated total daily meropenem requirement in these patients with acute renal failure and undergoing CVVH was 2,482 ± 321 mg. Based on these data, we conclude that patients with severe infections who are undergoing CVVH can be treated effectively with 1 g of meropenem every 8 h.

scholarly journals Recent Advances in Oxygen Electrocatalysts Based on Perovskite Oxides

Nanomaterials ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 1161 ◽  
Author(s):  
Jun Xu ◽  
Chan Chen ◽  
Zhifei Han ◽  
Yuanyuan Yang ◽  
Junsheng Li ◽  
...  
Keyword(s):  
High Performance ◽  
Low Cost ◽  
High Surface ◽  
High Surface Area ◽  
Precious Metals ◽  
Perovskite Oxides ◽  
Air Battery ◽  
Energy Conversion Devices ◽  
Further Development ◽  
Electrochemical Oxygen

Electrochemical oxygen reduction and oxygen evolution are two key processes that limit the efficiency of important energy conversion devices such as metal–air battery and electrolysis. Perovskite oxides are receiving discernable attention as potential bifunctional oxygen electrocatalysts to replace precious metals because of their low cost, good activity, and versatility. In this review, we provide a brief summary on the fundamentals of perovskite oxygen electrocatalysts and a detailed discussion on emerging high-performance oxygen electrocatalysts based on perovskite, which include perovskite with a controlled composition, perovskite with high surface area, and perovskite composites. Challenges and outlooks in the further development of perovskite oxygen electrocatalysts are also presented.

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