Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared ...Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared by incorporating vincristine with quinacrine together using the ammonium sulfate gradient loading procedure. For the pharmacokinetic study, Sprague-Dawley rats were divided into two groups: each rat in the Group Ⅰwas administered intravenously via tail vein as stealthy liposomal vincristine plus quinacrine, and the Group Ⅱ similarly given as a mixture solution of free vincristine plus free quinacrine. The concentrations of vincristine and quinacrine in plasma were measured by HPLC with diode array detection and fluorescence detection, respectively. Results The mean particle size of stealthy liposomes was 135.9 ±7.1 nm and the encapsulation efficiencies of stealthy liposomes were 〉 90% for vincristine, and 〉 85% for quinacrine, respectively. Administered as the stealthy vincristine plus quinacrine liposomes, the plasma exposures of both vincristine and quinacrine were significantly extended, and the mean concentrations of both vincristine and quinacrine were significantly higher compared to those given as the mixture solution of free vincristine plus free quinacrine. The Cmax, t1/2, AUC0-24 h values of vincristine for stealthy liposomal group were significantly increased, but the total clearance Cl values decreased, as compared to those of free drug group, respectively. Similarly, the Cmax, t1/2 and AUC0-24 h values of quinacrine for the stealthy liposomal group were significantly increased, but the total clearance C1 values decreased, as compared to those of free quinacrine. Conclusion The anti-resistant stealthy liposomes are successfully prepared by incorporating vincristine with quinacrine, and the liposomes extend significantly the duration in blood circulation and improve evidently the plasma concentrations of both vincristine and quinacrine.展开更多
The multiple antibiotic resistance regulatory protein(MarR) binds to two promoter sites on the marO operator in Escherichia coli.Our study showed that more than one MarR dimer proteins bound to either of its two promo...The multiple antibiotic resistance regulatory protein(MarR) binds to two promoter sites on the marO operator in Escherichia coli.Our study showed that more than one MarR dimer proteins bound to either of its two promoter sites(Site I and Site II),suggesting that MarR might form higher complexes than homodimers when bound to DNA inside E.coli cells.To further verify this hypothesis,we site-specifically incorporated a photocrosslinking probe at the interface between two MarR dimer proteins.Photolysis in living E.coli cells revealed a covalent linkage between the two interdimer subunits of MarR,suggesting that MarR forms dimer of dimers in vivo.展开更多
基金National Natural Science Foundation of China(No.30572260).
文摘Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared by incorporating vincristine with quinacrine together using the ammonium sulfate gradient loading procedure. For the pharmacokinetic study, Sprague-Dawley rats were divided into two groups: each rat in the Group Ⅰwas administered intravenously via tail vein as stealthy liposomal vincristine plus quinacrine, and the Group Ⅱ similarly given as a mixture solution of free vincristine plus free quinacrine. The concentrations of vincristine and quinacrine in plasma were measured by HPLC with diode array detection and fluorescence detection, respectively. Results The mean particle size of stealthy liposomes was 135.9 ±7.1 nm and the encapsulation efficiencies of stealthy liposomes were 〉 90% for vincristine, and 〉 85% for quinacrine, respectively. Administered as the stealthy vincristine plus quinacrine liposomes, the plasma exposures of both vincristine and quinacrine were significantly extended, and the mean concentrations of both vincristine and quinacrine were significantly higher compared to those given as the mixture solution of free vincristine plus free quinacrine. The Cmax, t1/2, AUC0-24 h values of vincristine for stealthy liposomal group were significantly increased, but the total clearance Cl values decreased, as compared to those of free drug group, respectively. Similarly, the Cmax, t1/2 and AUC0-24 h values of quinacrine for the stealthy liposomal group were significantly increased, but the total clearance C1 values decreased, as compared to those of free quinacrine. Conclusion The anti-resistant stealthy liposomes are successfully prepared by incorporating vincristine with quinacrine, and the liposomes extend significantly the duration in blood circulation and improve evidently the plasma concentrations of both vincristine and quinacrine.
基金supported by research grants from the National Natural Science Foundation of China(91013005, 21001010 and 20932006 to P.R.C.)National Key Basic Research Foundation of China(2010CB912300 to P.R.C.)
文摘The multiple antibiotic resistance regulatory protein(MarR) binds to two promoter sites on the marO operator in Escherichia coli.Our study showed that more than one MarR dimer proteins bound to either of its two promoter sites(Site I and Site II),suggesting that MarR might form higher complexes than homodimers when bound to DNA inside E.coli cells.To further verify this hypothesis,we site-specifically incorporated a photocrosslinking probe at the interface between two MarR dimer proteins.Photolysis in living E.coli cells revealed a covalent linkage between the two interdimer subunits of MarR,suggesting that MarR forms dimer of dimers in vivo.