摘要：In the present study, a chitosan-coated calcium phosphate nanoparticle（CS/CaP/sirNA NP） was developed to deliver si rNA for treatment of cervical cancer. The CS/CaP/sirNA NPs were prepared by the nano-precipitation method. The resulted NPs had a uniform spherical morphology with a size of ～194 nm and a zeta potential of ～＋27 mV. In vitro experiments demonstrated that these NPs could efficiently deliver si EGFr into Hela cells and significantly down-regulate the EGFr expression level, which was probably associated with enhanced cell adhesion of chitosan, leading to extended residence time of cell internalization. Then the internalized CS/CaP/sirNA NPs exhibited pH-responsive disassembly of NPs, resulting in the enhanced release of si rNA and rapid lysosomal escape into cytoplasm. Moreover, in vivo anticancer results showed that the CS/CaP/sirNA NPs had significant inhibitory effects on tumor growth after intratumoral injection in Hela tumor xenografted nude mice, accompanying with no obvious changes of body weight during the whole experimental period. All these results indicated that the CS/CaP/sirNA NPs would have great potential to deliver si rNA for the treatment of cervical cancer via mucosal administration.

摘要：In pre-clinical phase of new drug development,it is particularly important to establish an in vitro model to mimic the metabolism situation of human *** aim of the in vitro model is to reduce the usage of experimental animals and to make a more accurate prediction of the drug metabolism in *** chip is an emerging technology to establish predictive *** integrating subcellular fractions,hepatocytes or liver tissue in the microfluidic chips,more predictive in vitro metabolism models can be established for drug *** microfluidic platform offers dynamic and controlled fluids,as well as sophisticated liver tissue assembly to remodel the physiological and pathological microenvironment of liver in the human *** review updates the microfluidic-based liver drug metabolism models since 2011,and summarizes the development of different models based on different chip vectors(subcellular components,primary hepatocytes,and tissue sections).It serves as a guide for newcomers to this dynamic field.

摘要：目的研究治疗禽流感药物扎那米韦的合成工艺。方法以N-乙酰神经氨酸作为起始原料,经过酯化、酰化、成环、开环、叠氮化、还原、水解及AIMSA取代等8步反应制备扎那米韦。结果与结论经过对合成工艺的改进得到了目标产物,其结构经1H-NMr1、3C-NMr、Lr-MS、Hr-MS、元素分析和X-晶体衍射予以确证。总收率为10.1%。