Multidrug resistance (MDR) remains the major obstacle to the success of clinical cancer chemotherapy. P-glycoprotein (P-gp), encoded by the MDR1, is an important part with complex mechanisms associated with the MDR. In order to overcome the MDR of tumors, we in the present experimental design incorporated small interfering RNA (siRNA) targeting MDR1 gene and anticancer drug paclitaxel (PTX) into the solid lipid nanoparticles (SLNs) to achieve the combinational therapeutic effects of genetherapy and chemotherapy. In this study, siRNA-PTX-SLNs were successfully prepared. The cytotoxicity of blank SLNs and siRNA-PTX-SLNs in MCF-7 cells and MCF-7/ADR cells were detected by MTT; and the uptake efficiency of PTX in MCF-7/ADR cells were detected via HPLC method; quantitative real-time PCR and flow cytometry were performed to investigate the silencing effect of siRNA-PTX-SLNs on MDR1 gene in MCF-7/ADR cells. The results showed that PTX loaded SLNs could significantly inhibit the growth of tumor cells, and more importantly, the MDR tumor cells treated with siRNA-PTX-SLNs showed the lowest viability. HPLC study showed that SLNs could enhance the cellular uptake for PTX. Meanwhile, siRNA delivered by SLNs significantly decreased the P-gp expression in MDR tumor cells, thus increased the cellular accumulation of rhodamine123 as a P-gp substrate. In conclusion, the MDR1 gene could be silenced by siRNA-PTX-SLNs, which could promote the growth inhibition efficiency of PTX on tumor cells, leading to synergetic effect on MDR tumor therapy.
ObjectiveTo systematically review the quality of evidence-based guidelines (EBGs) on medication therapy for neonatal bacterial meningitis, and compare differences and similarities of the drugs recommended, in order to provide references for clinical application. MethodsDatabases such as the TRIP, PubMed, CNKI, VIP, WanFang, CBM, National Guideline Clearinghouse and Guidelines International Network were searched to collect evidence-based guidelines on medication therapy for neonatal bacterial meningitis. Methodological quality of included studies was assessed according to the AGREE Ⅱ instrument, and the differences and similarities among recommendations were compared. ResultsA total of 4 EBGs were included. Among them, one guideline was developed by the America and three guidelines were by the UK. Only one guideline was developed specially for neonates, while the rest were for neonates and children of different ages. According to the AGREE Ⅱ instrument, "scope and purpose", "stakeholder involvement", "rigor of development", "clarity and presentation", "applicability" and "editorial independence" were scored more than 60%. The recommendations of different guidelines were basically the same, only with conflicts in some areas. ConclusionAlthough most guidelines concerning neonatal bacterial meningitis are of high quality, grading levels of evidence and strength of recommendation should be unified.