A new compound named DHDK was isolated from Viscum coloratum and identified as (1E,4E)-1,7-bis(4-hydroxyphenyl)hepta -1,4-dien-3-one. DHDK, a new potential anti-tumor drug, was synthesized and prepared poly(ethylene g...A new compound named DHDK was isolated from Viscum coloratum and identified as (1E,4E)-1,7-bis(4-hydroxyphenyl)hepta -1,4-dien-3-one. DHDK, a new potential anti-tumor drug, was synthesized and prepared poly(ethylene glycol)-poly(D.L-lactic acid)(mPEG-PLA) micelles due to cytotoxic effects on a range of cancer cells. A revered phase liquid chromatographyic method has been developed and validated for the determination of potential related impurities in DHDK-loaded mPEG-PLA micelles. The micelles was subjected to the stress conditions of acid, base, oxidation, thermal and photolysis. The determination was achieved on Phenomenex SynergiTM 4 μm Fusion-RP 80?(250 mm × 4.6 mm, 4 μm) with a gradient elution and the detection wavelength was set at 220 nm. Regression analysis shows as r value (correlation coefficient) of greater than 0.999 for DHDK and six potential impurities. Recoveries of impurities were found between 90.0% and 108.0%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness, which can be used for determination of related impurities in DHDK-loaded mPEG-PLA micelles.展开更多
Novel mixed polymeric micelles formed by biocompatible polymers,mPEG-PLA and Pluronic P105,were fabricated and used as a nanocarrier to solubilize the poorly soluble anesthetic drug propofol.Propofol was added directl...Novel mixed polymeric micelles formed by biocompatible polymers,mPEG-PLA and Pluronic P105,were fabricated and used as a nanocarrier to solubilize the poorly soluble anesthetic drug propofol.Propofol was added directly to an aqueous solution of mPEG-PLA/Pluronic P105 mixed micelles and stirred into a micellar solution.The average particle size and size distribution of micelles were evaluated by the dynamic light scattering technology.Drug loading content,encapsulation efficiency and free drug concentration were determined by using ultracentrifugation and lyophilization.In vitro release characteristic of propofol formulation was investigated by dialysis method.The physical stability of mixed micelles was also assessed under storage condition（4 oC） after six months.Sleep-recovery studies in male Sprague-Dawley rats,at a dose of 10 mg/kg were performed to compare the pharmacodynamic profiles of propofol in mixed micelles with that of commercial lipid emulsion（CLE）.The results indicated that solubilization of propofol in the mixed micelles was more efficient than that in mPEG-PLA alone.Micelles with the optimized composition of mPEG-PLA/Pluronic P105/Propofol（10：4：5,w/w/w） had particle size of about 90 nm with narrow distribution（polydispersity index of about 0.2）.The content of free propofol in the aqueous phase of mixed micelles was significantly lower than that in CLE（P〈0.05）.There was no remarkable differences for particle size,polydispersity index,and free drug concentration when the mix micelles were stored at 4 oC for six months,suggesting that the propofol-loaded mixed micelles were stable for at least six months.The accumulative release of mixed micelles was significantly higher than that of CLE at the corresponding time points,suggesting that quick release rate for mixed micelles might produce favorable pharmacological effect.No significant differences in the unconsciousness time and recovery time of righting reflex were observed between the mixed micelles and CLE（P〉0.05）.In conclusion,the mixed micelle of mPEG-PLA and pluronic copolymer may be a promising candidate for intravenous delivery of propofol in clinic.展开更多
Nanoparticles with typical core-shell structure were prepared with a blend of methoxypoly（ethylene glycol）-poly（lactide） copolymer （MPEG-PLA） and poly （lactic acid） （PLA） along with paclitaxel by the O/W sol...Nanoparticles with typical core-shell structure were prepared with a blend of methoxypoly（ethylene glycol）-poly（lactide） copolymer （MPEG-PLA） and poly （lactic acid） （PLA） along with paclitaxel by the O/W solvent evaporation method. An orthogonal experiment L9（3）3 was applied to get the best preparation conditions. The core-shell paclitaxel-loaded MPEG-PLA/PLA nanoparticles with the highest drug loading efficiency were obtained when amount of MPEG-PLA, time of ultrasonication and volume of deionized water were 300 mg, 10 rain and 30 mL, respectively. The release behavior of paclitaxel from the optimal MPEG-PLA/PLA nanoparticles showed that 22% ofpaclitaxel was released in 14 d. When incubating with human nasopharyngeal carcinoma ceils expressing LMP 1, these optimal nanoparticles showed a little lower tumor growth compared with free paclitaxel.展开更多
文摘A new compound named DHDK was isolated from Viscum coloratum and identified as (1E,4E)-1,7-bis(4-hydroxyphenyl)hepta -1,4-dien-3-one. DHDK, a new potential anti-tumor drug, was synthesized and prepared poly(ethylene glycol)-poly(D.L-lactic acid)(mPEG-PLA) micelles due to cytotoxic effects on a range of cancer cells. A revered phase liquid chromatographyic method has been developed and validated for the determination of potential related impurities in DHDK-loaded mPEG-PLA micelles. The micelles was subjected to the stress conditions of acid, base, oxidation, thermal and photolysis. The determination was achieved on Phenomenex SynergiTM 4 μm Fusion-RP 80?(250 mm × 4.6 mm, 4 μm) with a gradient elution and the detection wavelength was set at 220 nm. Regression analysis shows as r value (correlation coefficient) of greater than 0.999 for DHDK and six potential impurities. Recoveries of impurities were found between 90.0% and 108.0%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness, which can be used for determination of related impurities in DHDK-loaded mPEG-PLA micelles.
基金National Development of Significant New Drugs(New Preparation and New Technology,Grant No. 2009zx09310-001)the National Basic Research Program of China (973 program,Grant No. 2009CB930300)
文摘Novel mixed polymeric micelles formed by biocompatible polymers,mPEG-PLA and Pluronic P105,were fabricated and used as a nanocarrier to solubilize the poorly soluble anesthetic drug propofol.Propofol was added directly to an aqueous solution of mPEG-PLA/Pluronic P105 mixed micelles and stirred into a micellar solution.The average particle size and size distribution of micelles were evaluated by the dynamic light scattering technology.Drug loading content,encapsulation efficiency and free drug concentration were determined by using ultracentrifugation and lyophilization.In vitro release characteristic of propofol formulation was investigated by dialysis method.The physical stability of mixed micelles was also assessed under storage condition（4 oC） after six months.Sleep-recovery studies in male Sprague-Dawley rats,at a dose of 10 mg/kg were performed to compare the pharmacodynamic profiles of propofol in mixed micelles with that of commercial lipid emulsion（CLE）.The results indicated that solubilization of propofol in the mixed micelles was more efficient than that in mPEG-PLA alone.Micelles with the optimized composition of mPEG-PLA/Pluronic P105/Propofol（10：4：5,w/w/w） had particle size of about 90 nm with narrow distribution（polydispersity index of about 0.2）.The content of free propofol in the aqueous phase of mixed micelles was significantly lower than that in CLE（P〈0.05）.There was no remarkable differences for particle size,polydispersity index,and free drug concentration when the mix micelles were stored at 4 oC for six months,suggesting that the propofol-loaded mixed micelles were stable for at least six months.The accumulative release of mixed micelles was significantly higher than that of CLE at the corresponding time points,suggesting that quick release rate for mixed micelles might produce favorable pharmacological effect.No significant differences in the unconsciousness time and recovery time of righting reflex were observed between the mixed micelles and CLE（P〉0.05）.In conclusion,the mixed micelle of mPEG-PLA and pluronic copolymer may be a promising candidate for intravenous delivery of propofol in clinic.
基金Key Research Foundation of Wannan Medical College(Grant No.WK2014Z06)Doctoral Starting-up Foundation of Wannan Medical College(Grant No.201219)
文摘Nanoparticles with typical core-shell structure were prepared with a blend of methoxypoly（ethylene glycol）-poly（lactide） copolymer （MPEG-PLA） and poly （lactic acid） （PLA） along with paclitaxel by the O/W solvent evaporation method. An orthogonal experiment L9（3）3 was applied to get the best preparation conditions. The core-shell paclitaxel-loaded MPEG-PLA/PLA nanoparticles with the highest drug loading efficiency were obtained when amount of MPEG-PLA, time of ultrasonication and volume of deionized water were 300 mg, 10 rain and 30 mL, respectively. The release behavior of paclitaxel from the optimal MPEG-PLA/PLA nanoparticles showed that 22% ofpaclitaxel was released in 14 d. When incubating with human nasopharyngeal carcinoma ceils expressing LMP 1, these optimal nanoparticles showed a little lower tumor growth compared with free paclitaxel.
