Aim The oxymatrine phospholipid complexs were prepared, and its activity against hepatitis B virus in vitro were studied. Methods Using tetrahydrofuran as a reaction medium, oxymatrine and phospholipids were resolved ...Aim The oxymatrine phospholipid complexs were prepared, and its activity against hepatitis B virus in vitro were studied. Methods Using tetrahydrofuran as a reaction medium, oxymatrine and phospholipids were resolved into the medium, Oxymatrine phospholipid eomplexs were prepared. The toxicity measurements and inhibitory effect on HBsAg, HBeAg, and HBVDNA of oxymatrine phospholipid complex in 2.2.15 cells were studied respectively. Results The content of oxymatrine in the phospholipids eomplexs prepared was 24,86% （W/W）. The TCO of the oxymatrine phospholipid eomplexs was 250 μmol·L^- 1 The inhibitory effect of HBsAg, HBeAg, HBV-DNA of 2.2.15 cells treated by oxymatrine phospholipid complex were higher than those of the oxymatrine. Conclusion Oxymatrine phospholipid complex can have stronger effective activity against hepatitis B virus compared with oxymatrine. So oxymatrine phospholipid eomplexs were showing its potential antiviral activity in hepatitis B treatment.展开更多
Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its ...Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its clinical applications.In the present study,phospholipid complex（PC） technology was employed to improve the solubility and bioavailability of HCPT.XRD data confirmed the formation of HCPT-PC.However,our previously prepared HCPT-PC is too sticky,which may result in the slow dissolution rate and negative effects on its absorption.Therefore,we prepared HCPT-PC-solid dispersion（HCPT-PC-SD）and lipid-based formulations of HCPT-PC through simple preparation process.The results showed that the dissolution rate of HCPT-PC was effectively improved by solid dispersion technology,which reached 91.73%in 45 min.Pharmacokinetic study revealed that the AUC_（0-t） of HCPT-PC-SD and HCPT-PC lipid-based formulations was effectively further increased compared with HCPT-PC.Moreover,we found that the combination of SD technology and lipid-base formulations could be a promising drug-delivery system to improve the oral bioavailability of HCPT-PC.In addition,we showed that the bioavailability of HCPT-PC lipid-base formulations was even greater than that of HCPT-PC-SD.In particular,lipid-base formulations could be prepared just by a simple method,suggesting its feasibility of industrialization.展开更多
Kaempferol(KA),as one of the flavonoids,has extensive pharmacological properties.However,the poor solubility of KA severely limits its clinical application.In our study,the kaempferol phospholipid complex(KA-PC)has be...Kaempferol(KA),as one of the flavonoids,has extensive pharmacological properties.However,the poor solubility of KA severely limits its clinical application.In our study,the kaempferol phospholipid complex(KA-PC)has been prepared by solvent evaporation for the enhancement of the bioavailability of KA.KA-PC was verified by scanning electron microscope characterization methods.Drug loading,solubility and long-term stability were measured.The characterization results showed that KA-PC was formed through the intermolecular interaction between KA and phospholipids.The solubility of KA-PC in water was 189 times higher than that of KA,and the solubility in n-octanol was also significantly improved.Besides,pharmacodynamic studies showed that KA-PC can significantly reduce the level of serum uric acid in mice without causing renal injury.This study expanded the clinical application of KA by preparing KA-PC.展开更多
Genistein phospholipid complex(GS-PC)was produced in order to increase the solubility and antioxidant activity of genistein(GS),an insoluble natural polyphenol compound.By using the solvent evaporation process,GS-PC w...Genistein phospholipid complex(GS-PC)was produced in order to increase the solubility and antioxidant activity of genistein(GS),an insoluble natural polyphenol compound.By using the solvent evaporation process,GS-PC was produced.Several characteristics techniques were used to confi rm the production of GS-PC,and its physicochemical characteristics and antioxidant activity were investigated.The outcome showed that GS-PC had a recombination rate of 96.84%±0.51%.The characterization results confi rmed that GS-PC was formed by the intermolecular interaction between GS and phospholipids.In vitro antioxidant studies showed that GS-PC had a certain scavenging ability on DPPH free radicals,ABTS free radicals and hydroxyl free radicals.In summary,the results of this study indicated that GS-PC could be used as a formula to improve its solubility and antioxidant activity.展开更多
Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholi...Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholipid complexes represents a promising approach to increase the oral bioavailability of active constituents, which is consist of ‘‘label-friendly'phospholipids and active constituents. Hydrogen bond interactions between active constituents and phospholipids enable phospholipid complexes as an integral part. This review provides an update on four important issues related to phyto-phospholipid complexes: active constituents, phospholipids, solvents, and stoichiometric ratios. We also discuss recent progress in research on the preparation, characterization, structural verification, and increased bioavailability of phyto-phospholipid complexes.展开更多
Background:Inhalation-based combination therapy has gained increasing attention for local treatments.However,a key challenge remains in ensuring the sustained pulmonary release of multiple active ingredients,particula...Background:Inhalation-based combination therapy has gained increasing attention for local treatments.However,a key challenge remains in ensuring the sustained pulmonary release of multiple active ingredients,particularly in traditional Chinese medicine(TCM)formulations.Objective:This study investigates a novel PulmoSphere-based inhalable carrier designed for the sustained pulmonary release of mul-tiple active ingredients,using Shuang-Huang-Lian as a model TCM formulation containing three chemical markers.Materials and methods:The carrier was developed using PulmoSphere technology,incorporating phospholipid complexes of the chemical markers and hyaluronic acid(HA)into spray-dried microparticles.The aerodynamic properties,release characteristics,pulmo-nary distribution,and anti-inflammatory efficacy of different formulations were evaluated in vitro and in mice.Results:The microparticles retained the excellent aerodynamic properties of conventional PulmoSphere particles,with a mass median aerodynamic diameter of approximately 3.1μm and a fine particle fraction of approximately 55%.Compared to free Shuang-Huang-Lian or phospholipid complex-loaded PulmoSphere particles,the HA-containing particles prolonged the retention of chemical markers in the lung epithelial lining fluid,demonstrating sustained release in vivo.Additionally,the HA-containing formulation enhanced the exposure of the three chemical markers to immune cells and lung tissues,leading to improved and prolonged anti-inflammatory effects,even at de-creased doses.Conclusion:This novel inhalable particle system represents a promising approach for sustained pulmonary co-delivery of multiple ac-tive ingredients,offering enhanced and extended local therapeutic efficacy.展开更多
The aim of this study was to develop a formulation to improve the oral absorption of baicalin(BA)by combining a phospholipid complex(PC)and self-emulsifying microemulsion drug delivery system(SMEDDS),termed BA–PC–SM...The aim of this study was to develop a formulation to improve the oral absorption of baicalin(BA)by combining a phospholipid complex(PC)and self-emulsifying microemulsion drug delivery system(SMEDDS),termed BA–PC–SMEDDS.BA–PC was prepared by a solvent evaporation method and evaluated by complexation percentage(CP).The physicochemical properties of BA–PC were determined.The synergistic effect of PC and SMEDDS on permeation of BA was studied in vitro with Caco-2 cells and in situ with a single pass intestinal perfusion model.The improved bioavailability of BA in BA–PC–SMEDDS was confirmed in an in vivo rat model.The CP of BA–PC reached 100%when the molar ratio of drug to phospholipid(PP)was Z1:1.The solubility of BA–PC increased in both water and octanol,and the log P o/w of BA–PC was increased significantly.BA–PC–SMEDDS could be dispersed more evenly in water,compared to BA and BA–PC.Both the Caco-2 cell uptake and single-pass intestinal perfusion models illustrated that transport of BA in BA–PC was lower than that of free BA,while improved significantly in BA–PC–SMEDDS.The relative bioavailability of BA–PC(1:2)–SMEDDS was 220.37%.The combination system of PC and SMEDDS had a synergistic effect on improving the oral absorption of BA.展开更多
Quercetin(QUE)has many beneficial biological activities and pharmacological actions in vitro.However,its oral bioavailability in vivo was very poor due to poor solubility,and severely restricted its clinical applicati...Quercetin(QUE)has many beneficial biological activities and pharmacological actions in vitro.However,its oral bioavailability in vivo was very poor due to poor solubility,and severely restricted its clinical applications.In this study,we prepared quercetin solid dispersion(QUE-SD)and quercetin phospholipids complex solid dispersion(QUE-PC-SD)by a solvent evaporation method to improve the absorption of QUE in vivo.The results of XRD of QUE-SD and QUE-PC-SD showed that QUE was dispersed homogeneously in an amorphous or molecular state in QUE-SD and QUE-PC-SD,which could contribute to improve the solubility and dissolution of QUE.The solubility of QUE-SD and QUE-PC-SD was enhanced from(4.03±0.02)μg/mL to(26.91=1=0.06)μg/mL and(30.65±0.06)μg/mL,respectively.The solubility of QUE-PC-SD was higher than that of QUE-SD.In vitro dissolution study,it was showed that the maximum dissolution of QUE(9.57%)from the QUE-SD and QUE-PC-SD was enhanced to 93.81%and 94.16%,respectively.The results of pharmacokinetic experiment indicated that the QUE-SD and QUE-PC-SD exhibited considerable enhancement in the oral bioavailability.The relative bioavailability of QUE-SD and QUE-PC-SD compared with QUE were 149.49%and 198.32%,respectively.In addition,the relative bioavailability of QUE-PC-SD was also higher than that of QUE-SD.Therefore,in regard to drugs with poor solubility and low permeation,an active constituent-PC-SD system could result to a better absorption and higher bioavailability.展开更多
文摘Aim The oxymatrine phospholipid complexs were prepared, and its activity against hepatitis B virus in vitro were studied. Methods Using tetrahydrofuran as a reaction medium, oxymatrine and phospholipids were resolved into the medium, Oxymatrine phospholipid eomplexs were prepared. The toxicity measurements and inhibitory effect on HBsAg, HBeAg, and HBVDNA of oxymatrine phospholipid complex in 2.2.15 cells were studied respectively. Results The content of oxymatrine in the phospholipids eomplexs prepared was 24,86% （W/W）. The TCO of the oxymatrine phospholipid eomplexs was 250 μmol·L^- 1 The inhibitory effect of HBsAg, HBeAg, HBV-DNA of 2.2.15 cells treated by oxymatrine phospholipid complex were higher than those of the oxymatrine. Conclusion Oxymatrine phospholipid complex can have stronger effective activity against hepatitis B virus compared with oxymatrine. So oxymatrine phospholipid eomplexs were showing its potential antiviral activity in hepatitis B treatment.
基金Science and Technology Department of Henan province Fund Project(Grant No.144300510019)
文摘Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its clinical applications.In the present study,phospholipid complex（PC） technology was employed to improve the solubility and bioavailability of HCPT.XRD data confirmed the formation of HCPT-PC.However,our previously prepared HCPT-PC is too sticky,which may result in the slow dissolution rate and negative effects on its absorption.Therefore,we prepared HCPT-PC-solid dispersion（HCPT-PC-SD）and lipid-based formulations of HCPT-PC through simple preparation process.The results showed that the dissolution rate of HCPT-PC was effectively improved by solid dispersion technology,which reached 91.73%in 45 min.Pharmacokinetic study revealed that the AUC_（0-t） of HCPT-PC-SD and HCPT-PC lipid-based formulations was effectively further increased compared with HCPT-PC.Moreover,we found that the combination of SD technology and lipid-base formulations could be a promising drug-delivery system to improve the oral bioavailability of HCPT-PC.In addition,we showed that the bioavailability of HCPT-PC lipid-base formulations was even greater than that of HCPT-PC-SD.In particular,lipid-base formulations could be prepared just by a simple method,suggesting its feasibility of industrialization.
基金funded by Young and Middle Aged Teachers’Career Development Support Project of Shenyang Pharmaceutical University(ZQN2019005).
文摘Kaempferol(KA),as one of the flavonoids,has extensive pharmacological properties.However,the poor solubility of KA severely limits its clinical application.In our study,the kaempferol phospholipid complex(KA-PC)has been prepared by solvent evaporation for the enhancement of the bioavailability of KA.KA-PC was verified by scanning electron microscope characterization methods.Drug loading,solubility and long-term stability were measured.The characterization results showed that KA-PC was formed through the intermolecular interaction between KA and phospholipids.The solubility of KA-PC in water was 189 times higher than that of KA,and the solubility in n-octanol was also significantly improved.Besides,pharmacodynamic studies showed that KA-PC can significantly reduce the level of serum uric acid in mice without causing renal injury.This study expanded the clinical application of KA by preparing KA-PC.
文摘Genistein phospholipid complex(GS-PC)was produced in order to increase the solubility and antioxidant activity of genistein(GS),an insoluble natural polyphenol compound.By using the solvent evaporation process,GS-PC was produced.Several characteristics techniques were used to confi rm the production of GS-PC,and its physicochemical characteristics and antioxidant activity were investigated.The outcome showed that GS-PC had a recombination rate of 96.84%±0.51%.The characterization results confi rmed that GS-PC was formed by the intermolecular interaction between GS and phospholipids.In vitro antioxidant studies showed that GS-PC had a certain scavenging ability on DPPH free radicals,ABTS free radicals and hydroxyl free radicals.In summary,the results of this study indicated that GS-PC could be used as a formula to improve its solubility and antioxidant activity.
文摘Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholipid complexes represents a promising approach to increase the oral bioavailability of active constituents, which is consist of ‘‘label-friendly'phospholipids and active constituents. Hydrogen bond interactions between active constituents and phospholipids enable phospholipid complexes as an integral part. This review provides an update on four important issues related to phyto-phospholipid complexes: active constituents, phospholipids, solvents, and stoichiometric ratios. We also discuss recent progress in research on the preparation, characterization, structural verification, and increased bioavailability of phyto-phospholipid complexes.
基金supported by the National Natural Science Foundation of China(Grant No.82173983)the CAMS Innovation Fund for Medical Sciences(CIFMS,Grant No.2021-I2M-1-048).
文摘Background:Inhalation-based combination therapy has gained increasing attention for local treatments.However,a key challenge remains in ensuring the sustained pulmonary release of multiple active ingredients,particularly in traditional Chinese medicine(TCM)formulations.Objective:This study investigates a novel PulmoSphere-based inhalable carrier designed for the sustained pulmonary release of mul-tiple active ingredients,using Shuang-Huang-Lian as a model TCM formulation containing three chemical markers.Materials and methods:The carrier was developed using PulmoSphere technology,incorporating phospholipid complexes of the chemical markers and hyaluronic acid(HA)into spray-dried microparticles.The aerodynamic properties,release characteristics,pulmo-nary distribution,and anti-inflammatory efficacy of different formulations were evaluated in vitro and in mice.Results:The microparticles retained the excellent aerodynamic properties of conventional PulmoSphere particles,with a mass median aerodynamic diameter of approximately 3.1μm and a fine particle fraction of approximately 55%.Compared to free Shuang-Huang-Lian or phospholipid complex-loaded PulmoSphere particles,the HA-containing particles prolonged the retention of chemical markers in the lung epithelial lining fluid,demonstrating sustained release in vivo.Additionally,the HA-containing formulation enhanced the exposure of the three chemical markers to immune cells and lung tissues,leading to improved and prolonged anti-inflammatory effects,even at de-creased doses.Conclusion:This novel inhalable particle system represents a promising approach for sustained pulmonary co-delivery of multiple ac-tive ingredients,offering enhanced and extended local therapeutic efficacy.
基金This work was supported by grants from the National Natural Science Foundation of China(No.30973953C1909)。
文摘The aim of this study was to develop a formulation to improve the oral absorption of baicalin(BA)by combining a phospholipid complex(PC)and self-emulsifying microemulsion drug delivery system(SMEDDS),termed BA–PC–SMEDDS.BA–PC was prepared by a solvent evaporation method and evaluated by complexation percentage(CP).The physicochemical properties of BA–PC were determined.The synergistic effect of PC and SMEDDS on permeation of BA was studied in vitro with Caco-2 cells and in situ with a single pass intestinal perfusion model.The improved bioavailability of BA in BA–PC–SMEDDS was confirmed in an in vivo rat model.The CP of BA–PC reached 100%when the molar ratio of drug to phospholipid(PP)was Z1:1.The solubility of BA–PC increased in both water and octanol,and the log P o/w of BA–PC was increased significantly.BA–PC–SMEDDS could be dispersed more evenly in water,compared to BA and BA–PC.Both the Caco-2 cell uptake and single-pass intestinal perfusion models illustrated that transport of BA in BA–PC was lower than that of free BA,while improved significantly in BA–PC–SMEDDS.The relative bioavailability of BA–PC(1:2)–SMEDDS was 220.37%.The combination system of PC and SMEDDS had a synergistic effect on improving the oral absorption of BA.
基金National Science and Technology Major Projects “Major New Drugs Innovation and Development”(Grant No.2018ZX09201019-002-009)
文摘Quercetin(QUE)has many beneficial biological activities and pharmacological actions in vitro.However,its oral bioavailability in vivo was very poor due to poor solubility,and severely restricted its clinical applications.In this study,we prepared quercetin solid dispersion(QUE-SD)and quercetin phospholipids complex solid dispersion(QUE-PC-SD)by a solvent evaporation method to improve the absorption of QUE in vivo.The results of XRD of QUE-SD and QUE-PC-SD showed that QUE was dispersed homogeneously in an amorphous or molecular state in QUE-SD and QUE-PC-SD,which could contribute to improve the solubility and dissolution of QUE.The solubility of QUE-SD and QUE-PC-SD was enhanced from(4.03±0.02)μg/mL to(26.91=1=0.06)μg/mL and(30.65±0.06)μg/mL,respectively.The solubility of QUE-PC-SD was higher than that of QUE-SD.In vitro dissolution study,it was showed that the maximum dissolution of QUE(9.57%)from the QUE-SD and QUE-PC-SD was enhanced to 93.81%and 94.16%,respectively.The results of pharmacokinetic experiment indicated that the QUE-SD and QUE-PC-SD exhibited considerable enhancement in the oral bioavailability.The relative bioavailability of QUE-SD and QUE-PC-SD compared with QUE were 149.49%and 198.32%,respectively.In addition,the relative bioavailability of QUE-PC-SD was also higher than that of QUE-SD.Therefore,in regard to drugs with poor solubility and low permeation,an active constituent-PC-SD system could result to a better absorption and higher bioavailability.
