bTrichosporon asahii is one of the important opportunistic pathogenic fungi. Here, we first report the draft nuclear chromosome genome sequence and mitochondrial genome sequence of T. asahii CBS 2479, which is a standard strain of T. asahii that was isolated from a progressive psoriatic lesion. COG analysis predicted that 3,131 genes were assigned to 23 functional categories and that 628 genes were predicted to have a general function.
The toxicity and side effects of traditional chemotherapeutic drugs are the main causes of chemotherapy failure. To improve the specificity and selectivity of chemotherapeutic drugs for tumor cells, a novel redox-sensitive polymer prodrug, polyethylene glycol-poly (β-benzyl-L-aspartate) (PEG-PBLA)-SS-paclitaxel (PPSP), was designed and synthesized in this study. The PPSP micelle was manufactured via high-speed dispersion stirring and dialysis. The particle size and zeta potential of this prodrug micelle were 63.77 ± 0.91 nm and −25.8 ± 3.24 mV, respectively. The micelles were uniformly distributed and presented a spherical morphology under a transmission electron microscope. In the tumor physiological environment, the particle size of the PPSP micelles and the release rate of paclitaxel (PTX) were significantly increased compared with those of mPEG-PBLA-CC-PTX (PPCP) micelles, reflecting the excellent redox-sensitive activity of the PPSP micelles. The inhibitory effect of PPSP on HepG2, MCF-7 and HL-7702 cell proliferation was investigated with MTT assays, and the results demonstrated that PPSP is superior to PTX with respect to the inhibition of two tumor cell types at different experimental concentration. Simultaneously PPSP has lower toxicity against HL-7702 cells then PTX and PPCP. Moreover, the blank micelle from mPEG-PBLA showed no obvious toxicity to the two tumor cells at different experimental concentrations. In summary, the redox-sensitive PPSP micelle significantly improved the biosafety and the anti-tumor activity of PTX.
Background
Amphotericin B (AMB) is a polyene antibiotic with broad spectrum antifungal activity, but its clinical toxicities and poor solubility limit the wide application of AMB in clinical practice. Recently, new drug-loaded nanoparticles (NPs) – diblock copolymer D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (PLGA-TPGS) – have received special attention for their reduced toxicity, and increased effectiveness of drug has also been reported. This study aimed to develop AMB-loaded PLGA-TPGS nanoparticles (AMB-NPs) and evaluate their antifungal effects in vitro and in vivo.
Methods
AMB-NPs were prepared with a modified nanoprecipitation method and then characterized in terms of physical characteristics, in vitro drug release, stability, drug-encapsulation efficiency, and toxicity. Finally, the antifungal activity of AMB-NPs was investigated in vitro and in vivo.
Results
AMB-NPs were stable and spherical, with an average size of around 110 nm; the entrapment efficacy was closed to 85%, and their release exhibited a typically biphasic pattern. The actual minimum inhibitory concentration of AMB-NPs against
Candida albicans
was significantly lower than that of free AMB, and AMB-NPs were less toxic on blood cells. In vivo experiments indicated that AMB-NPs achieved significantly better and prolonged antifungal effects when compared with free AMB.
Conclusion
The AMB-PLGA-TPGS NP system significantly improves the AMB bioavailability by improving its antifungal activities and reducing its toxicity, and thus, these NPs may become a good drug carrier for antifungal treatment.
The carbonylative Suzuki–Miyaura reaction between aryl tosylates/triflates with arylboronic acid is herein reported, using base-free conditions and a balloon pressure of carbon monoxide.
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