Selective Cellular Uptake and Cytotoxicity of Curcumin-encapsulated SPC and HSPC Liposome Nanoparticles on Human Bladder Cancer Cells.

BACKGROUND: Curcumin is a main bioactive constituent of turmeric (Curcuma longa L.) with pleiotropic health beneficial effects. However, poor bioavailability is the major barrier to the efficient pharmacological effects of curcumin in humans. AIMS: The present study aimed to develop liposome formulations based on soybean phosphatidylcholine (SPC) and hydrogenated SPC (HSPC) to enhance the bioavailability of curcumin in bladder cancer cells. METHODS: Curcumin was encapsulated in HSPC and SPC liposome nanoparticles using the solvent evaporation method. Physical properties, encapsulation efficiency (%), stability, and in vitro drug release of the prepared liposome formulations have been evaluated. The cellular uptake and cytotoxicity of curcumin-encapsulated nanoliposomes on bladder carcinoma HTB9 cell line and normal fibroblast L929 cell line were studied. DNA fragmentation, apoptosis, and genotoxicity assessments have been carried out to determine the molecular mechanisms underlying the cytotoxic effects of liposomal curcumin formulations on bladder cancer cells. RESULTS: The results indicated that curcumin could be efficiently encapsulated in the HSPC and SPC liposome formulations. The liposomal curcumin formulations have shown shelf-life stability for 14 weeks at 4°C. The accelerated stability testing showed that curcumin encapsulated in nanoliposomes was significantly (p < 0.001) more stable than free curcumin at various pH degrees ranging from alkaline to acidic pH. The in vitro drug release study showed curcumin to be sustainably released from the liposome nanoparticles. Of note, SPC and HSPC nanoliposome formulations significantly increased the cellular uptake and cytotoxicity of curcumin on bladder cancer HTB9 cells. Mechanistically, liposomal curcumin was found to exert a selective inhibitory effect on the viability of cancer cells by inducing apoptosis and DNA damage. CONCLUSION: In conclusion, SPC and HSPC liposome nanoparticles can significantly increase the stability and bioavailability of curcumin, which are important for improving its pharmacological effect.

A simple, sensitive and rapid isocratic reversed-phase high-performance liquid chromatography method for determination and stability study of curcumin in pharmaceutical samples.

OBJECTIVE: This study was designed to develop and validate a new reversed-phase high-performance liquid chromatography (RP-HPLC) method based on Q2 (R1) International Conference on Harmonization (ICH) guideline for determination of curcumin in pharmaceutical samples. MATERIALS AND METHODS: The HPLC instrument method was optimized with isocratic elution with acetonitrile: ammonium acetate (45:55, v/v, pH 3.5), C18 column (150 mm×4.6 mm×5 µm particle size) and a flow rate of 1 ml/min in ambient condition and total retention time of 17 min. The volume of injection was set at 20 µl and detection was recorded at 425 nm. The robustness of the method was examined by changing the mobile phase composition, mobile phase pH, and flow rate. RESULTS: The method was validated with respect to precision, accuracy and linearity in a concentration range of 2-100 µg/ml. The limit of detection (LOD) and limit of quantification (LOQ) were 0.25 and 0.5 µg/ml, respectively. The percentage of recovery was 98.9 to 100.5 with relative standard deviation (RSD) < 0.638%. CONCLUSION: The method was found to be simple, sensitive and rapid for determination of curcumin in pharmaceutical samples and had enough sensitivity to detect degradation product of curcumin produced under photolysis and hydrolysis stress condition.

Effects of ethanolic extract of green tea on decreasing the level of lipid profile in rat.

OBJECTIVE: The aim of the present study was to elucidate the possible biochemical improving effect in lipid metabolic that may result from continuous treatment with Green Tea extract in normal albino rats and those rendered hyperlipidemic by long term supplementation of fat-enriched diet. MATERIALS AND METHODS: Fifty male albino rats aged six weeks with 200±10 g weight were randomly divided into five groups: Group A (negative control), groups B (positive control), Group C (treatment with drug), Group D (treatment with extract), and Group E (prevention with extract). All groups except Group A were received fat-enriched diet throughout the study. Group C received 25 mg/kg/day of the nicotinic acid from day 28 to the end of study. Group D was also treated with 100 mg/kg/day of the extract from day 28 to the end of study and finally group E was also treated with 100 mg/kg/day of the extract from the start of the study to the end. Lipid levels were determined weekly. Data were expressed as mean±SEM which were calculated using SigmaPlot® software. The obtained data were statistically analyzed using Student's t-test. RESULTS: In group (D), total cholesterol, LDLc, HDLc, and triglyceride levels were significantly decreased by 33.3%, 30.2%, 40%, respectively, compared with the group C (p<0.001 ). There was no significant difference in lipid profile in group E through the study. Nicotinic acid in group C decreased the serum levels of all measured parameters (p<0.001). The body weight of animals in treated groups with extract (groups D & E) were decreased by 8% (p<0.01). CONCLUSION: The results of this study demonstrated that the extract of green tea has a hyperlipidemic lowering effect.

New sesquiterpene coumarin from the roots of Ferula latisecta.

OBJECTIVE: The genus of Ferula belongs to the tribe Peucedaneae, subfamily of Apioideae and family of Umbelliferae with 133 species distributed throughout the Mediterranean area and central Asia, especially in the former USSR and neighboring countries such as Iran. The popular Persian name of the most of these species is "Koma". In this research we tried to isolate and elucidate the structure of new sesquiterpene in the root of Ferula latisecta (F. latisecta). MATERIALS AND METHODS: Dried and powdered roots of F. latisecta were extracted with CH2Cl2 using a Soxhlet apparatus. The extract was concentrated in vacuo to give a red extract. The extract was subjected to column chromatography on silica gel. (1)H NMR, (13)C NMR, DEPT, (1)H-(1)H COSY, HMBC, HSQC, and NOESY spectra were the methods we used to elucidate the structure of new sesquiterpene in this plant. RESULTS: One new sesquieterpene coumarin, namely Latisectin and IUPAC name [1-(2-Hydroxy-4-methoxy-phenyl)-3,4,8,12-tetramethyl-trideca-4,7,11-trien-1-one ] , together with one known compound , Kopetdaghin C, were isolated from the root of F. latisecta. CONCLUSION: In this research the structure of one new and one known sesquiterpene in the root of F. latisecta was elucidated.