FLT3-specific curcumin micelles enhance activity of curcumin on FLT3-ITD overexpressing MV4-11 leukemic cells

Curcumin, a major active compound in the turmeric rhizome, has many biological properties, especially anti-leukemia activity. The overexpression of FMS-like tyrosine kinase 3 protein with internal tandem duplication (FLT3-ITD) mutation protein was related to the poor prognosis and disease progression of leukemia. In this study, the cytotoxicity and inhibitory effect of curcumin on cell cycle of FLT3-ITD overexpressing MV4-11 leukemic cells were evaluated. Moreover, curcumin polymeric micelles conjugated with FLT3-specific peptide (FLT3-Cur-micelles) were prepared using a film hydration method to increase curcumin solubility and the inhibitory effect on MV4-11 cells was evaluated. Cytotoxicity and cell cycle analysis were performed using an MTT assay and flow cytometry, respectively. Physical properties of FLT3-Cur-micelles, including particle size, size distribution, morphology, and entrapment efficiency (EE), were evaluated. Cellular uptake of the micelles on MV4-11 cells was determined by flow cytometry and fluorescence microscopy. FLT3-Cur-micelles were observed with size less than 50?nm and high EE of >75%. In addition, FLT3-Cur-micelles demonstrated excellent internalization and increased curcumin accumulation in leukemic cells when compared to free curcumin. Furthermore, FLT3-Cur-micelles exhibited a strong cytotoxic effect on MV4-11 cells with IC₅₀ value of 1.1?µM, whereas the blank micelles showed no effect. Furthermore, FLT3-Cur-micelles showed no significant effect on normal human PBMCs with IC₅₀ value >25?µM. In summary, FLT3-Cur-micelles are a promising nanocarrier system for enhancing anti-leukemic activity of curcumin and suitable for further preclinical studies.     

Spectrofluorimetric determination of tranexamic acid in hydrogel patch formulations by derivatization with naphthalene-2, 3-dicarboxaldehyde/cyanide

The aim of this research was to develop and validate a spectrofluorimetric method for determination of tranexamic acid in hydrogel patch formulations. Tranexamic acid ( trans -4-aminomethylcyclohexanecarboxylic acid, trans -AMCHA) is an antifibrinolytic drug that recently gained attention as a skin-whitening agent due to its inhibitory effect on ultraviolet (UV)-induced pigmentation in vivo. Derivatization with naphthalene-2, 3-dicarboxaldehyde (NDA) in the presence of cyanide ion (CN^-) to produce a fluorescent 1-cyanobenz[ f ]isoindole (CBI) product (?ex = 420 nm, ?em = 480 nm) [[Au: Please check the symbol.]] is for the first time reported for the determination of tranexamic acid in hydrogel patch formulations. Other separation techniques were not used in the analysis of the CBI-fluorescent product as required in the previous studies. The developed method was proven to be precise and accurate with percent recoveries ranging between 98.0% and 101.8% at the concentration range of 8.4–84.0 μg/ml (R² > 0.999). The intra-and inter-day precisions as expressed by the relative standard deviations (RSD) were below 1.85%. Derivatization of tranexamic acid with NDA/CN^-was completed within 5 min and was stable for at least 30 min. The method has been applied to the analysis of drug content and release profiles in tranexamic hydrogel patch formulations.     

Comparison of antioxidant capacities and cytotoxicities of certain fruit peels

This work was undertaken to explore the potential of fruit waste materials as sources of powerful natural antioxidants. The peels of eight kinds of fruits commonly consumed and grown in Thailand were used. The ethanolic fruit peel extracts were subjected to the scavenging tests of DPPH and ABTS radicals. Results from both assays were in good agreement that the top three markedly high free radical-scavenging power was from the peel extracts of Punica granatum (pomegranate), Nephelium lappaceum (rambutan), and Garcinia mangostana (mangosteen). The IC₅₀ values to quench the DPPH free radicals of these three extracts were 0.003, 0.006, and 0.023 mg/ml and the trolox equivalent antioxidant capacity (TEAC) values from ABTS assay were 4.066, 3.074, and 3.001 mM/mg, respectively. The extract of mangosteen peel showed moderate toxicity to Caco-2 cells and high toxicity to peripheral blood mononuclear cells (PBMC) with the IC₅₀ values of 32.0 and 4.9 μg/ml, respectively. Pomegranate peel extract stimulated Caco-2 cell and PBMC proliferation with the ED₅₀ of 4.7 and 44.4 μg/ml, respectively. Peel extract of rambutan exhibited extremely high value of IC₅₀ (>100 μg/ml) against both cell types indicating non-toxic activity to the cells. It was concluded that the peel of rambutan may be considered potentially useful as a source of natural antioxidants for food or drug product because of its high antioxidant activity and non-toxic property to normal cells.