Aim To prepare and characterize the QURC-HP-β-CD inclusion complexes and investigate the thermodynamic parameters of the process. Methods QURC-HP-β-CD inclusion complexes were prepared by the grinding method. The eq...Aim To prepare and characterize the QURC-HP-β-CD inclusion complexes and investigate the thermodynamic parameters of the process. Methods QURC-HP-β-CD inclusion complexes were prepared by the grinding method. The equilibrium inclusion constants and thermodynamic parameters were determinated by phase solubility analysis. Dissolution tests were performed to study the dissolution rate of inclusion complexes. The formation of inclusion complexes was confirmed by differential scanning calorimetry （ DSC）, infrared spectroscopy （IR） , powder X-ray diffractometry （PXRD） and scanning electron microscopy （SEM）. Results The aqueous solubility of quercetin was greatly increased （ about 37 folds） by inclusion technique, and the initial dissolution rate was markedly improved （10 folds） in the first 5 min. The results of DSC and SEM photographs showed that quercetin crystal disappeared in inclusion complexes, which indicated the formation of new phase. FT-IR spectra showed that the carbonyl quercetin crystal grinding method. absorption band of quercetin was shifted. PXRD showed that the diffraction peak of disappeared. Conclusion QURC-HP-β-CD inclusion complexes are produced by the The solubility of quercetin is improved by the inclusion technique.展开更多
The objective of this study was to prepare and characterize paclitaxel-polyvinylpyrrolidone （PTX-PVP） solid dispersions with the intention of improving its solubility and dissolution properties. The PTX-PVP solid di...The objective of this study was to prepare and characterize paclitaxel-polyvinylpyrrolidone （PTX-PVP） solid dispersions with the intention of improving its solubility and dissolution properties. The PTX-PVP solid dispersion systems were prepared by solvent method. The release rate ofpaclitaxel was determined from dissolution studies and the physicochemical properties of solid dispersion were investigated by differential scanning calorimetry （DSC）, powder X-ray diffraction （PXRD） and scanning electron microscopy （SEM）. The cytotoxicities ofpaclitaxel in solid dispersion to the SKOV-3 cells were assayed by a SRB staining method. The results showed that the solubility and dissolution rate of paclitaxel were significantly improved in solid dispersion system compared with that of the pure drug and physical mixture. The results of DSC and PXRD showed that the paclitaxel in solid dispersion was amorphous form. No paclitaxel crystals in the solid dispersions was found during SEM analysis. Cytotoxicity study suggested that the inhibitory rates of PTX-PVP solid dispersion to SKOV-3 cells were higher than that of pure paclitaxel. The solubility and dissolution of paclitaxel were improved by solid dispersion technique. In vitro cytotoxicity of paclitaxel in solid dispersion was higher than that of pure drug.展开更多
Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin （9-NC ME） for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in term...Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin （9-NC ME） for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC ME were evaluated. 9-NC ME was intravenously administered via tail vein in healthy rats. Results A stable microemulsion was formulated consisted of soybean oil as oil phase, EPC/Tween-80 as emulsifier, and anhydrous ethanol as co-emulsifier. The droplets of the microemulsion were spherical shape with mean diameter of 38.3 ± 4.0 nm after 1：20 dilution with 5% glucose injection. The pharmacokinetic parameters of 9-NC ME after intravenous administration in rats were t1/2 of 0.97 ± 0.14 h, A UC0-8 of 372.77 ±49.62 ng·h·mL^-1 and MRT of 1.40 ± 0.21 h which were 1.4-fold, 1.65-fold, and 1.4-fold more than those of 9-NC solution （P〈0.01）. Conclusion The results suggested that 9-NC ME was a promising drug delivery system and it was expected to provide a novel 9-NC injection for cancer patients.展开更多
Aim Peptides as ligands have shown the active targeting properties to the receptors like integrins, a family of receptors over-expressed in cancers. The present study was to develop and characterize two peptides modif...Aim Peptides as ligands have shown the active targeting properties to the receptors like integrins, a family of receptors over-expressed in cancers. The present study was to develop and characterize two peptides modified drug-containing liposomes. Methods Argine-glycine-aspartic acid （RGD） tripeptide and glycine-argine-glycine-aspartic acid-serine （GRGDS） pentapeptide were used for modifications on the doxorubicin-loaded sterically stabilized liposomes （SSL-doxorubicin） for the liposome preparation, RGD-SSL-doxorubicin and GRGDS-SSL-doxorubicin, respectively. Characterizations were performed by measurements of the encapsulation efficiency, particle size and zeta potential, release rates in a simulated in vivo environment, and cytotoxicity to ovarian cancer cells. Cell uptake was investigated by flow cytometry and confocal microscopy methods. Results All encapsulation efficiencies of the liposomes were above 95%, and the modifications using RGD or GRGDS did not affect the final encapsulation efficiency. Average particle sizes of the liposomes Were in the range between 105.7 ± 3.5 nm and 130.5 ± 3.0 nm, and zeta potential values were between -3.3 ± 0.3 and -6.1 ± 0.3 mV. Approximately 2/5 of doxorubicin was released from liposomes before 12 h in the simulated in vivo environment containing fetal bovine serum. Inhibitory rates to cancer cells of the modified liposomes were slightly lower as compared to free doxorubicin. Similar phenomena were observed in the uptake measured by flow cytometry and confocal assay. After uptake applying various formulations on the cancer cells, doxorubicin was mainly distributed in the nuclei of SKOV-3 cells. Conclusion Two new doxorubicin-contained liposomes were successfully prepared and modified with argine-glycine-aspartic acid （RGD） tripeptide and glycine-argine-glycine- aspartic acid-serine （GRGDS） pentapeptide. In vitro characterization indicated that modifications did not alter significantly the properties of the sterically stabilized liposomes.展开更多
In this study, the novel RGD-modified stabilized cationic liposomes were developed as the delivery vehicle for siRNA targeting human MDR1 gene. The complex of cationic liposomes and siRNA, RGD-Lipo-siRNA, was prepared...In this study, the novel RGD-modified stabilized cationic liposomes were developed as the delivery vehicle for siRNA targeting human MDR1 gene. The complex of cationic liposomes and siRNA, RGD-Lipo-siRNA, was prepared with a narrow size distribution below 200 nm. It was shown that the encapsulated siRNA in the liposomes could be effectively protected from serum degradation. Also, enhanced cell binding and intracellular uptake of siRNA in the doxorubicin-resistant human ova- rian cancer cell lines SKOV3/A were found in RGD-Lipo-siRNA preparation as compared to that of unmodified cationic lipsomes （Lipo-siRNA）. Using the post-insertion method for RGD modification, lysosome release of siRNA in pRGD-Lipo-siRNA was improved. From flow cytometry, significant increase of doxorubicin accumulation was observed in the SKOV3/A cells treated with pRGD-Lipo-siRNA targeting human MDR1 gene. In vitro cytotoxicity assay showed that the significant cell growth inhibition was achieved in the SKOV3/A cells after treating with the combined use of siRNA and doxorubicin. In conclusions, postinserted RGD modified lipoplex, pRGD-Lipo-siRNA, was successfully used for siRNA transfection and achieved drug resistance reversal in human ovarian cancer SKOV3/A （doxorubicin-resistant） cells. It suggested that this liposomes might be a potential vehicle for siRNA delivery in vivo.展开更多
文摘2024年3月7日,北京大学药学院天然药物及仿生药物全国重点实验室王坚成教授/朱元军博士团队和北京大学第三医院运动医学江东主任医师团队共同在国际学术期刊ACS Nano在线发表了题为“Nanomedicines Promote Cartilage Regeneration in Osteoarthritis by Synergistically Enhancing Chondrogenesis of Mesenchymal Stem Cells and Regulating Inflammatory Environment”的研究论文。该研究提出了碳酸酐酶IX siRNA(siCA9)调控炎症微环境调控促进Kartogenin(KGN)诱导的间充质干细胞(MSCs)软骨定向分化作用的新策略,显著提高了MSCs在骨关节炎(OA)治疗中的软骨再生能力,改善了晚期OA治疗效应。
文摘Aim To prepare and characterize the QURC-HP-β-CD inclusion complexes and investigate the thermodynamic parameters of the process. Methods QURC-HP-β-CD inclusion complexes were prepared by the grinding method. The equilibrium inclusion constants and thermodynamic parameters were determinated by phase solubility analysis. Dissolution tests were performed to study the dissolution rate of inclusion complexes. The formation of inclusion complexes was confirmed by differential scanning calorimetry （ DSC）, infrared spectroscopy （IR） , powder X-ray diffractometry （PXRD） and scanning electron microscopy （SEM）. Results The aqueous solubility of quercetin was greatly increased （ about 37 folds） by inclusion technique, and the initial dissolution rate was markedly improved （10 folds） in the first 5 min. The results of DSC and SEM photographs showed that quercetin crystal disappeared in inclusion complexes, which indicated the formation of new phase. FT-IR spectra showed that the carbonyl quercetin crystal grinding method. absorption band of quercetin was shifted. PXRD showed that the diffraction peak of disappeared. Conclusion QURC-HP-β-CD inclusion complexes are produced by the The solubility of quercetin is improved by the inclusion technique.
文摘The objective of this study was to prepare and characterize paclitaxel-polyvinylpyrrolidone （PTX-PVP） solid dispersions with the intention of improving its solubility and dissolution properties. The PTX-PVP solid dispersion systems were prepared by solvent method. The release rate ofpaclitaxel was determined from dissolution studies and the physicochemical properties of solid dispersion were investigated by differential scanning calorimetry （DSC）, powder X-ray diffraction （PXRD） and scanning electron microscopy （SEM）. The cytotoxicities ofpaclitaxel in solid dispersion to the SKOV-3 cells were assayed by a SRB staining method. The results showed that the solubility and dissolution rate of paclitaxel were significantly improved in solid dispersion system compared with that of the pure drug and physical mixture. The results of DSC and PXRD showed that the paclitaxel in solid dispersion was amorphous form. No paclitaxel crystals in the solid dispersions was found during SEM analysis. Cytotoxicity study suggested that the inhibitory rates of PTX-PVP solid dispersion to SKOV-3 cells were higher than that of pure paclitaxel. The solubility and dissolution of paclitaxel were improved by solid dispersion technique. In vitro cytotoxicity of paclitaxel in solid dispersion was higher than that of pure drug.
基金National Natural Science Foundation of China (GrantNo.30430760)the 985 projects (Phase II) of the State Key Labo-ratory of Natural and Biomimetic Drugs (Peking University, China).
文摘Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin （9-NC ME） for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC ME were evaluated. 9-NC ME was intravenously administered via tail vein in healthy rats. Results A stable microemulsion was formulated consisted of soybean oil as oil phase, EPC/Tween-80 as emulsifier, and anhydrous ethanol as co-emulsifier. The droplets of the microemulsion were spherical shape with mean diameter of 38.3 ± 4.0 nm after 1：20 dilution with 5% glucose injection. The pharmacokinetic parameters of 9-NC ME after intravenous administration in rats were t1/2 of 0.97 ± 0.14 h, A UC0-8 of 372.77 ±49.62 ng·h·mL^-1 and MRT of 1.40 ± 0.21 h which were 1.4-fold, 1.65-fold, and 1.4-fold more than those of 9-NC solution （P〈0.01）. Conclusion The results suggested that 9-NC ME was a promising drug delivery system and it was expected to provide a novel 9-NC injection for cancer patients.
基金National Natural Science Foundation of China(Grant No. 30572261)the 985 Projects (Phase II) of theState Key Laboratory of Natural and Biomimetic Drugs(Peking University, China).
文摘Aim Peptides as ligands have shown the active targeting properties to the receptors like integrins, a family of receptors over-expressed in cancers. The present study was to develop and characterize two peptides modified drug-containing liposomes. Methods Argine-glycine-aspartic acid （RGD） tripeptide and glycine-argine-glycine-aspartic acid-serine （GRGDS） pentapeptide were used for modifications on the doxorubicin-loaded sterically stabilized liposomes （SSL-doxorubicin） for the liposome preparation, RGD-SSL-doxorubicin and GRGDS-SSL-doxorubicin, respectively. Characterizations were performed by measurements of the encapsulation efficiency, particle size and zeta potential, release rates in a simulated in vivo environment, and cytotoxicity to ovarian cancer cells. Cell uptake was investigated by flow cytometry and confocal microscopy methods. Results All encapsulation efficiencies of the liposomes were above 95%, and the modifications using RGD or GRGDS did not affect the final encapsulation efficiency. Average particle sizes of the liposomes Were in the range between 105.7 ± 3.5 nm and 130.5 ± 3.0 nm, and zeta potential values were between -3.3 ± 0.3 and -6.1 ± 0.3 mV. Approximately 2/5 of doxorubicin was released from liposomes before 12 h in the simulated in vivo environment containing fetal bovine serum. Inhibitory rates to cancer cells of the modified liposomes were slightly lower as compared to free doxorubicin. Similar phenomena were observed in the uptake measured by flow cytometry and confocal assay. After uptake applying various formulations on the cancer cells, doxorubicin was mainly distributed in the nuclei of SKOV-3 cells. Conclusion Two new doxorubicin-contained liposomes were successfully prepared and modified with argine-glycine-aspartic acid （RGD） tripeptide and glycine-argine-glycine- aspartic acid-serine （GRGDS） pentapeptide. In vitro characterization indicated that modifications did not alter significantly the properties of the sterically stabilized liposomes.
基金National Natural Science Foundation of China(Grant No.30701056)Foundation of MOST(973 Program,Grant No.2007CB935801)+1 种基金Beijing Natural Science Foundation of China(Grant No.7083112)Doctoral Foundation of Ministry of Education of China(Grant No.20070001813).
文摘In this study, the novel RGD-modified stabilized cationic liposomes were developed as the delivery vehicle for siRNA targeting human MDR1 gene. The complex of cationic liposomes and siRNA, RGD-Lipo-siRNA, was prepared with a narrow size distribution below 200 nm. It was shown that the encapsulated siRNA in the liposomes could be effectively protected from serum degradation. Also, enhanced cell binding and intracellular uptake of siRNA in the doxorubicin-resistant human ova- rian cancer cell lines SKOV3/A were found in RGD-Lipo-siRNA preparation as compared to that of unmodified cationic lipsomes （Lipo-siRNA）. Using the post-insertion method for RGD modification, lysosome release of siRNA in pRGD-Lipo-siRNA was improved. From flow cytometry, significant increase of doxorubicin accumulation was observed in the SKOV3/A cells treated with pRGD-Lipo-siRNA targeting human MDR1 gene. In vitro cytotoxicity assay showed that the significant cell growth inhibition was achieved in the SKOV3/A cells after treating with the combined use of siRNA and doxorubicin. In conclusions, postinserted RGD modified lipoplex, pRGD-Lipo-siRNA, was successfully used for siRNA transfection and achieved drug resistance reversal in human ovarian cancer SKOV3/A （doxorubicin-resistant） cells. It suggested that this liposomes might be a potential vehicle for siRNA delivery in vivo.
