Aim To investigate the combined effect of hydroxypropyl-β-cyclodextrin （HP-β-CD） and media pH on the solubility of prostaglandin E1 （PGE1） and construct a theoretical equation for the drug solubility as a functi...Aim To investigate the combined effect of hydroxypropyl-β-cyclodextrin （HP-β-CD） and media pH on the solubility of prostaglandin E1 （PGE1） and construct a theoretical equation for the drug solubility as a function of HP-β-CD concentration and media pH. Methods The solubility of PGE1 under different pH conditions was determined. Then, the drug solubility in different concentrations of HP-β-CD acidic or pH neutral solutions was measured, respectively. Finally, a theoretical solubility equation for the drug as a function of HP-β-CD concentration and media pH was deduced and confirmed in experiment. Results PGEs was solubilized by HP-β-CD or by increasing media pH. The drug solubility as a function of HP-β-CD concentration was found to follow the AL-type complexation model in acidic or neutral pH media, suggesting that both the ionized and neutral drugs form 1：1 molecular ratio complexes. Conclusions The solubility of PGE1 may be improved by increasing media pH or by using HP-β-CD as a solubilizer. HP-β-CD and media pH can produce combined effect on the solubility of PGE1. The deduced equation for the drug solubility in this study effectively characterizes the roles of HP-β-CD and media pH in determining total solubility of the drug.展开更多
The biosynthesis of prostaglandins and thromboxanes has been a focus of interest in the management of many liver diseases.Cyclooxygenases are the enzymes involved in the first step of the biosynthesis of these lipid m...The biosynthesis of prostaglandins and thromboxanes has been a focus of interest in the management of many liver diseases.Cyclooxygenases are the enzymes involved in the first step of the biosynthesis of these lipid mediators and selective inhibitors for these isoenzymes as well as pharmacological analogues of prostaglandins have been developed and are currently applied therapeutically.Here we discuss the implications of these enzymes in the onset of metabolic and lipid disorders in the liver and their potential role in the progression of the diseases towards fibrosis and hepatocellular carcinogenesis.展开更多
文摘Aim To investigate the combined effect of hydroxypropyl-β-cyclodextrin （HP-β-CD） and media pH on the solubility of prostaglandin E1 （PGE1） and construct a theoretical equation for the drug solubility as a function of HP-β-CD concentration and media pH. Methods The solubility of PGE1 under different pH conditions was determined. Then, the drug solubility in different concentrations of HP-β-CD acidic or pH neutral solutions was measured, respectively. Finally, a theoretical solubility equation for the drug as a function of HP-β-CD concentration and media pH was deduced and confirmed in experiment. Results PGEs was solubilized by HP-β-CD or by increasing media pH. The drug solubility as a function of HP-β-CD concentration was found to follow the AL-type complexation model in acidic or neutral pH media, suggesting that both the ionized and neutral drugs form 1：1 molecular ratio complexes. Conclusions The solubility of PGE1 may be improved by increasing media pH or by using HP-β-CD as a solubilizer. HP-β-CD and media pH can produce combined effect on the solubility of PGE1. The deduced equation for the drug solubility in this study effectively characterizes the roles of HP-β-CD and media pH in determining total solubility of the drug.
基金MINECO,Spain,No.SAF2014-52492RCOOPB20213(CSIC)+2 种基金No.SAF2013-43713R and No.SAF2016-75004RISCIII,Spain,CIBERcv and CIBERehdFEDER for financial support
文摘The biosynthesis of prostaglandins and thromboxanes has been a focus of interest in the management of many liver diseases.Cyclooxygenases are the enzymes involved in the first step of the biosynthesis of these lipid mediators and selective inhibitors for these isoenzymes as well as pharmacological analogues of prostaglandins have been developed and are currently applied therapeutically.Here we discuss the implications of these enzymes in the onset of metabolic and lipid disorders in the liver and their potential role in the progression of the diseases towards fibrosis and hepatocellular carcinogenesis.
