Urinary phospholipids are shown to be sensitive biomarkers for kidney injury. Many works have been reported on qualitative analysis of phospholipids and relative components in human urine while quantitative analysis i...Urinary phospholipids are shown to be sensitive biomarkers for kidney injury. Many works have been reported on qualitative analysis of phospholipids and relative components in human urine while quantitative analysis is rare. We have therefore developed a reliable and convenient quantitative method to evaluate the accuracy and specificity of dipalmitoylphosphatidylcholine （DPPC） as a biomarker for kidney injury diagnosis. Chromatographic separation was achieved using a HILIC Silica Column （2.1 ram^50 mm, 5 p.m）. Gradient elution was performed with 5 mM ammonium formate （0.1% formic acid） and acetonitrile （0.1% formic acid）, at a flow rate of 0.3 mL/min. This method was validated in a linear range of 2-200 ng/mL DPPC with inter-day precision of less than 6.5% and accuracy within 111.2% in human urine. Recovery rate, stability, dilution effect and matrix effect also met the requirements for drug evaluation and research issued by FDA. As the first HPLC-MS/MS method for quantitative determination of DPPC, it has been successfully applied to determine levels of DPPC in clinical urine samples and evaluated for potential use in the measurement of DPPC as a biomarker for kidney injury.展开更多
Delivering pharmacologic agents directly into the brain has been proposed as a means of bypassing the blood brain barrier.However,despite 16 years of research on a number of central nervous system disorders,an effecti...Delivering pharmacologic agents directly into the brain has been proposed as a means of bypassing the blood brain barrier.However,despite 16 years of research on a number of central nervous system disorders,an effective treatment using this strategy has only been observed in the brain tumor glioblastoma multiforme.Within this study we propose a novel system for delivering drugs into the brain named the simple diffusion (SDD) system.To validate this technique,rats were subjected to a single intracranial (at the caudate nucleus),or intraperitoneal injection,of the compound citicoline,followed two hours later by a permanent middle cerebral artery occlusion (pMCAO).Results showed that 12 h after pMCAO,with 0.0025 g kg-1 citicoline,an infarct volume 1/6 the size of the intraperitoneal group was achieved with a dose 1/800 of that required for the intraperitoneal group.These results suggest that given the appropriate injection point,through SDD a pharmacologically effective concentration of citicoline can be administered.展开更多
Hesperetin,an abundant bioactive component of citrus fruits,is poorly water-soluble,resulting in low oral bioavailability.We developed new formulations to improve the water solubility,antioxidant activity,and oral abs...Hesperetin,an abundant bioactive component of citrus fruits,is poorly water-soluble,resulting in low oral bioavailability.We developed new formulations to improve the water solubility,antioxidant activity,and oral absorption of hesperetin.Two nano-based formulations were developed,namely hesperetin-TPGS(D-α-tocopheryl polyethylene glycol 1000 succinate)micelles and hesperetin-phosphatidylcholine(PC)complexes.These two formulations were prepared by a simple technique called solvent dispersion,using US Food and Drug Administration(FDA)-approved excipients for drugs.Differential scanning calorimetry(DSC)and dynamic light scattering(DLS)were used to characterize the formulations’physical properties.Cytotoxicity analysis,cellular antioxidant activity assay,and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations.The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility,which increased to 21.5-and 20.7-fold,respectively.The hesperetin-TPGS micelles had a small particle size of 26.19 nm,whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm.In addition,the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2-and 3.9-fold,respectively.Importantly,the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration(Cmax)from 2.64μg/mL to 20.67 and 33.09μg/mL and also increased the area under the concentration–time curve of hesperetin after oral administration to 16.2-and 18.0-fold,respectively.The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin,indicating these formulations’potential applications in drugs and healthcare products.展开更多
文摘Urinary phospholipids are shown to be sensitive biomarkers for kidney injury. Many works have been reported on qualitative analysis of phospholipids and relative components in human urine while quantitative analysis is rare. We have therefore developed a reliable and convenient quantitative method to evaluate the accuracy and specificity of dipalmitoylphosphatidylcholine （DPPC） as a biomarker for kidney injury diagnosis. Chromatographic separation was achieved using a HILIC Silica Column （2.1 ram^50 mm, 5 p.m）. Gradient elution was performed with 5 mM ammonium formate （0.1% formic acid） and acetonitrile （0.1% formic acid）, at a flow rate of 0.3 mL/min. This method was validated in a linear range of 2-200 ng/mL DPPC with inter-day precision of less than 6.5% and accuracy within 111.2% in human urine. Recovery rate, stability, dilution effect and matrix effect also met the requirements for drug evaluation and research issued by FDA. As the first HPLC-MS/MS method for quantitative determination of DPPC, it has been successfully applied to determine levels of DPPC in clinical urine samples and evaluated for potential use in the measurement of DPPC as a biomarker for kidney injury.
基金supported by the National Natural Science Foundation of China(Grant Nos. 30972811 and 81071148)Natural Science Foundation of Beijing(Grant No. 7093137)
文摘Delivering pharmacologic agents directly into the brain has been proposed as a means of bypassing the blood brain barrier.However,despite 16 years of research on a number of central nervous system disorders,an effective treatment using this strategy has only been observed in the brain tumor glioblastoma multiforme.Within this study we propose a novel system for delivering drugs into the brain named the simple diffusion (SDD) system.To validate this technique,rats were subjected to a single intracranial (at the caudate nucleus),or intraperitoneal injection,of the compound citicoline,followed two hours later by a permanent middle cerebral artery occlusion (pMCAO).Results showed that 12 h after pMCAO,with 0.0025 g kg-1 citicoline,an infarct volume 1/6 the size of the intraperitoneal group was achieved with a dose 1/800 of that required for the intraperitoneal group.These results suggest that given the appropriate injection point,through SDD a pharmacologically effective concentration of citicoline can be administered.
基金Project supported by the National Natural Science Foundation of China(Nos.51773176,51522304,and U1501243)the Natural Science Foundation of Zhejiang Province(No.LY17H300002),China
文摘Hesperetin,an abundant bioactive component of citrus fruits,is poorly water-soluble,resulting in low oral bioavailability.We developed new formulations to improve the water solubility,antioxidant activity,and oral absorption of hesperetin.Two nano-based formulations were developed,namely hesperetin-TPGS(D-α-tocopheryl polyethylene glycol 1000 succinate)micelles and hesperetin-phosphatidylcholine(PC)complexes.These two formulations were prepared by a simple technique called solvent dispersion,using US Food and Drug Administration(FDA)-approved excipients for drugs.Differential scanning calorimetry(DSC)and dynamic light scattering(DLS)were used to characterize the formulations’physical properties.Cytotoxicity analysis,cellular antioxidant activity assay,and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations.The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility,which increased to 21.5-and 20.7-fold,respectively.The hesperetin-TPGS micelles had a small particle size of 26.19 nm,whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm.In addition,the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2-and 3.9-fold,respectively.Importantly,the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration(Cmax)from 2.64μg/mL to 20.67 and 33.09μg/mL and also increased the area under the concentration–time curve of hesperetin after oral administration to 16.2-and 18.0-fold,respectively.The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin,indicating these formulations’potential applications in drugs and healthcare products.
