ABSTRACT
A multiple-stimuli-responsive drug-conjugated cross-linked micelles was prepared by radical copolymerization. The chemical structure, morphology, and size of the cross-linked micelles were characterized, and the drug loading of the micelle was calculated. The experimental results indicated that the hydrodynamic size of the drug-loaded micelles were about 100 nm, and the as prepared micelles could be degraded and swelled in presence of reducing glutathione (GSH). The low critical solution temperature (LCST) of the micelle was around 39.4℃. According to the experimental results, the micelles will shrink at temperature above the LCST. Subsequently, the accumulative drug release rate was up to 91.78% under acidic (pH 5.0), reductive (GSH 10 mmol/L) and high temperature (42.0℃) conditions mimicking the tumor microenvironment, while a relatively low release rate of 1.12% was observed without stimulation. The drug-conjugated cross-linked micelles showed a strong cell uptake behavior. In the cytotoxicity assay, the micelles exhibited effective anti-cancer activity and excellent biocompatibility. In brief, the experimental results show that the as-prepared drug-conjugated cross-linked micelle exhibits multiple stimuli-responsiveness, which holds great promise for anti-cancer drug delivery.
ABSTRACT
OBJECTIVE: To prepare butenafine hydrochloride thermosensitive microemulsion-based hydrogel and evaluate the quality. METHODS: A series of temperature sensitive microemulsion gels with different gelation temperatures were prepared, using ethyl oleate as oil phase, Tween 80 as surfactant, ethanol as co-surfactant, and poloxamer as temperature-sensitive material. The morphology, particle size, Zeta potential, percutaneous absorption speed and skin retention were evaluated. RESULTS: The best formulation was composed of ethyl oleate-Tween 80-ethanol-poloxamer 407-poloxamer 188-distilled water at ratios of 4∶15∶10∶16.33∶5.68∶71. The oil/water microemulsion exhibited a spherical shape without adhesion or aggregation observed by TEM. The average diameter was 91.03 nm and the PDI was 0.246. The transdermal speed of microemulsion gel was faster than the marketed cream, and the drug retention in the skin was 5 times of the marketed cream. CONCLUSION: The hydrogel exhibits good temperature sensitivity and skin retention effect, and can penetrate skin cutin and act as a depot thus increase the local drug concentration and enhance the antibacterial effect.
ABSTRACT
In an attempt to understand the mechanism of aging in relation to the differences in enzyme regulation, the induction and kinetic properties of NADP+ -isocitrate dehydrogenase of the liver of immature (6 weeks), mature (13 weeks), adult (33 weeks) and old (85 weeks) female rats were studied. The specific activity of the cytoplasmic and mitochondrial NADP+ -isocitrate dehydrogenase increased up to the adult age (33 weeks) and decreased in the old rats (85 weeks). Overiectomy decreased and estradiol administration induced activity of both the mitochondrial and eytoplasmic enzyme in the liver ol immature, mature and adult rats but had no significant effect in old rats. However, the activity of mitochondrial NADP+ -isocitrate dehydrogenase decreased and eytoplasmic NADP+ -isocitrate dehydrogenase increased following ovariectomy in old rats (85 weeks). Hormone-mediated induction of enzyme activity was actinomycin D sensitive. The Km for isocitrate and NADP, Ki value for oxalomalate, heat stability and electrophoretic mobility of the purified enzyme from the cytosol fraction of the liver of immature and old rats were similar. It can he concluded that the enzyme does not change structurally with age.