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
Vitamin E( VE) is an ideal antioxidant and a stabilizing agent in biological membranes. In this study,silk fibroin( SF) /hydroxybutyl chitosan( HBC) nanofibrous scaffolds are loaded with VE tocopherol polyethylene gly...Vitamin E( VE) is an ideal antioxidant and a stabilizing agent in biological membranes. In this study,silk fibroin( SF) /hydroxybutyl chitosan( HBC) nanofibrous scaffolds are loaded with VE tocopherol polyethylene glycol 1000 succinate( VE TPGS) via electrospinning. SEM images show that the average nanofibrous diameter has no significant difference when the content of VE TPGS increases to 4. 0%( SF / HBC). However,the average nanofibrous diameter decreases largely to 200 nm when the VE TPGS content reaches 6. 0%. Furthermore,VE TPGS presents a sustained release behavior from the nanofibrous scaffolds. Cell viability studies of mouse skin fibroblasts( L929) demonstrate that VE TPGS loaded SF / HBC nanofibrous scaffolds present good cellular compatibility.Moreover,the incorporation of VE TPGS could strengthen the ability of SF / HBC nanofibrous scaffolds on protecting the cells against oxidation stress using the Tertbutyl hydroperoxide( t-BHP)-induced oxidative injury model. Therefore,VE TPGS-loaded SF /HBC nanofibrous scaffolds might be potential candidates for personal skin care,wound dressing and skin tissue engineering scaffolds.展开更多
为延长盐酸吉西他滨(1)的半衰期、提高生物利用度,采用逆相蒸发法制备聚乙二醇1000维生素E琥珀酸酯(TPGS)修饰的1脂质体(1-LP),并考察其性质和在大鼠体内的药动学行为。结果表明,所得1-LP的粒径为(212.6±7.2)nm、z电位为(-31.1...为延长盐酸吉西他滨(1)的半衰期、提高生物利用度,采用逆相蒸发法制备聚乙二醇1000维生素E琥珀酸酯(TPGS)修饰的1脂质体(1-LP),并考察其性质和在大鼠体内的药动学行为。结果表明,所得1-LP的粒径为(212.6±7.2)nm、z电位为(-31.1±2.9)m V、包封率为(70.56±1.92)%、载药量为(7.41±0.05)%。绘制了1-LP和1水溶液在p H 7.4磷酸盐缓冲液中的体外释药曲线,并用几种常用模型拟合试验数据。结果二者的释药数据均用双指数模型拟合效果较好(R^2为0.996和0.947)。对比研究了SD大鼠尾静脉注射给予1-LP或市售1注射液后的药动学行为。血浆中的药物浓度采用HPLC法测定。所得主要药动学参数为:t_(1/2)(4.12±0.73)和(1.32±0.10)h,AUC_(0→∞)(37.57±1.09)和(9.64±0.20)mg·L·h^(-1),MRT_(0→∞)(6.06±0.28)和(1.67±0.04)h。展开更多
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.
基金the Independent Design Project of Key Scientific and Technological Innovation Team of Zhejiang Province,China(No.2010R50012-19)the Key Student Research Training Project of Jiaxing University,China(No.851713022)+1 种基金Technology Commission of JiaxingM unicipality Program,China(No.2012AY1030)National Natural Science Foundation of China(No.31271035)
文摘Vitamin E( VE) is an ideal antioxidant and a stabilizing agent in biological membranes. In this study,silk fibroin( SF) /hydroxybutyl chitosan( HBC) nanofibrous scaffolds are loaded with VE tocopherol polyethylene glycol 1000 succinate( VE TPGS) via electrospinning. SEM images show that the average nanofibrous diameter has no significant difference when the content of VE TPGS increases to 4. 0%( SF / HBC). However,the average nanofibrous diameter decreases largely to 200 nm when the VE TPGS content reaches 6. 0%. Furthermore,VE TPGS presents a sustained release behavior from the nanofibrous scaffolds. Cell viability studies of mouse skin fibroblasts( L929) demonstrate that VE TPGS loaded SF / HBC nanofibrous scaffolds present good cellular compatibility.Moreover,the incorporation of VE TPGS could strengthen the ability of SF / HBC nanofibrous scaffolds on protecting the cells against oxidation stress using the Tertbutyl hydroperoxide( t-BHP)-induced oxidative injury model. Therefore,VE TPGS-loaded SF /HBC nanofibrous scaffolds might be potential candidates for personal skin care,wound dressing and skin tissue engineering scaffolds.
文摘为延长盐酸吉西他滨(1)的半衰期、提高生物利用度,采用逆相蒸发法制备聚乙二醇1000维生素E琥珀酸酯(TPGS)修饰的1脂质体(1-LP),并考察其性质和在大鼠体内的药动学行为。结果表明,所得1-LP的粒径为(212.6±7.2)nm、z电位为(-31.1±2.9)m V、包封率为(70.56±1.92)%、载药量为(7.41±0.05)%。绘制了1-LP和1水溶液在p H 7.4磷酸盐缓冲液中的体外释药曲线,并用几种常用模型拟合试验数据。结果二者的释药数据均用双指数模型拟合效果较好(R^2为0.996和0.947)。对比研究了SD大鼠尾静脉注射给予1-LP或市售1注射液后的药动学行为。血浆中的药物浓度采用HPLC法测定。所得主要药动学参数为:t_(1/2)(4.12±0.73)和(1.32±0.10)h,AUC_(0→∞)(37.57±1.09)和(9.64±0.20)mg·L·h^(-1),MRT_(0→∞)(6.06±0.28)和(1.67±0.04)h。
