Abstract. Tetrandrine (TET) is a poorly water-soluble bisbenzylisoquinoline alkaloid. In this study, TET solid lipid nanoparticles (SLNs) were prepared by a melt-emulsification and ultrasonication technique. Precirol ® ATO 5, glyceryl monostearate, and stearic acid were used as the lipid matrix for the SLNs, while Lipoid E80, Pluronic F68, and sodium deoxycholate were used as emulsifying and stabilizing agents. The physicochemical characteristics of the TET-SLNs were investigated when it was found that the mean particle size and zeta potential of the TET-SLNs were 134±1.3 nm and −53.8±1.7 mV, respectively, and the entrapment efficiency (EE) was 89.57%±0.39%. Differential scanning calorimetry indicated that TET was in an amorphous state in SLNs. TET-SLNs exhibited a higher release rate at a lower pH and a lower release rate at a higher pH. The release pattern of the TET-SLNs followed the Weibull model. The pharmacokinetics of TET-SLNs after intravenous administration to male rats was studied. TET-SLN resulted in a higher plasma concentration and lower clearance. The biodistribution study indicated that TET-SLN showed a high uptake in reticuloendothelial system organs. In conclusion, TET-SLNs with a small particle size, and high EE, can be produced by the method described in this study. The SLN system is a promising approach for the intravenous delivery of tetrandrine.
Backgroung: Tumor microenvironment (TME) has gradually emerged as an important research topic in the fight against cancer. The immune system is a major contributing factor in TME, and investigations have revealed that tumors are partially infiltrated with numerous immune cell subsets.Method: We obtained transcriptome RNA-seq data from the the Cancer Genome Atlas databases for 521 patients with colon adenocarcinoma (COAD). ESTIMATE algorithms are then used to estimate the fraction of stromal and immune cells in COAD samples.Result: A total of 1109 stromal-immune score-related differentially expressed genes were identified and used to generate a highconfidence protein-protein interaction network and univariate COX regression analysis. C-X-C motif chemokine 10 (CXCL10) was identified as the core gene by intersection analysis of data from protein-protein interaction network and univariate COX regression analysis. Then, for CXCL10, we performed gene set enrichment analysis, survival analysis and clinical analysis, and we used CIBERSORT algorithms to estimate the proportion of tumor-infiltrating immune cells in COAD samples.
Conclusion:We discovered that CXCL10 levels could be effective for predicting the prognosis of COAD patients as well as a clue that the status of TME is transitioning from immunological to metabolic activity, which provided additional information for COAD therapies.Abbreviations: COAD = colon adenocarcinoma, CRC = colorectal cancer, CXCL10 = C-X-C motif chemokine 10, DEGs = differentially expressed genes, GO = gene ontology, GSEA = gene set enrichment analysis, KEGG = Kyoto Encyclopedia of Genes and Genomes, M = metastasis, N = lymph node staging, PPI = protein-protein interaction, T = tumor infiltration depth, TCGA = the Cancer Genome Atlas, TICs = tumor-infiltrating immune cells, TME = tumor microenvironment.
The REB-NSs prepared by the combining method exhibited a higher plasma drug concentration and superior GI distribution, thereby demonstrating positive results for preparing nanosuspensions of local effective BCS IV drugs with pH dependence such as REB by this method.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.