[Show abstract][Hide abstract] ABSTRACT: In this study, a pH and temperature dual-sensitive liposome gel based on a novel cleavable hydrazone-based pH-sensitive methoxy polyethylene glycol 2000-hydrazone-cholesteryl hemisuccinate (mPEG-Hz-CHEMS) polymer was used for vaginal administration.
The pH-sensitive, cleavable mPEG-Hz-CHEMS was designed as a modified pH-sensitive liposome that would selectively degrade under locally acidic vaginal conditions. The novel pH-sensitive liposome was engineered to form a thermogel at body temperature and to degrade in an acidic environment.
A dual-sensitive liposome gel with a high encapsulation efficiency of arctigenin was formed and improved the solubility of arctigenin characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. The dual-sensitive liposome gel with a sol-gel transition at body temperature was degraded in a pH-dependent manner, and was stable for a long period of time at neutral and basic pH, but cleavable under acidic conditions (pH 5.0). Arctigenin encapsulated in a dual-sensitive liposome gel was more stable and less toxic than arctigenin loaded into pH-sensitive liposomes. In vitro drug release results indicated that dual-sensitive liposome gels showed constant release of arctigenin over 3 days, but showed sustained release of arctigenin in buffers at pH 7.4 and pH 9.0.
This research has shed some light on a pH and temperature dual-sensitive liposome gel using a cleavable mPEG-Hz-CHEMS polymer for vaginal delivery.
International Journal of Nanomedicine 05/2012; 7:2621-30. DOI:10.2147/IJN.S31757 · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In search of more effective antifungal agents, twenty-two new fluconazole derivatives containing 4-methyl phenol and thymine have been designed and synthesized based on the previous results of computer-aided drug design. All the derivatives retain the essential pharmacophore of fluconazole. Their structures are elucidated by H-1 NMR, elemental analysis and EST-MS. Preliminary in vitro antifungal activities bioassay showed that compound 51 exhibits better in vitro antifungal activities against eight fungi except Aspergillus fumigatus (7544) than fluconazole, compounds 5a similar to 5e, 5g, 5h, 7a and 7b show only moderate in vitro antifungal activities against different fungus. The introduction of propargyl group to nitrogen atom can enhance in vitro antifungal activities of this type derivative and it is worth of further research.
Chinese Journal of Organic Chemistry 05/2012; 32(5):922. DOI:10.6023/cjoc1107241 · 0.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The octillol-type derivatives 3 and its epimer 4 had been designed and synthesized from 20(S)-panaxadiol. The structures of 3 and 4 were confirmed by ESI-MS, 1 H-NMR, 13 C-NMR and X-ray diffraction. The crystal data showed the configuration of C-24 of two epimers as R-form (3) and S-form (4, epimer) respectively. Compound 3 was evaluated in vitro for its protective effect on cultured myocardiocytes with anoxia/reoxygen injury and compound 4 had none of this activity.