Pharmaceutical Sciences
Volume:16 Issue: 4, 2011

In the present study, effects of hydroalcoholic extract of grape seed (GSE) on ischemia-reperfusion (I/R)- induced infarct size and cardiac arrhythmias were investigated in isolated rat heart. Isolated rat hearts were divided into four groups and mounted on a Langendorff apparatus at constant pressure, then subjected to 30 min regional ischemia followed by 120 min reperfusion. In control group, the hearts were perfused by a modified Krebs-Henseleit solution throughout the experiment, however, in the test groups they were perfused by enriched Krebs solution with GSE (1, 10 and 100 μg/ml) during I/R. The ECGs were recorded and analyzed to determine cardiac arrhythmias. Infarct size was determined by computerized planimetry method. The results demonstrated that perfusion of GSE produces significant reduction in infarct size in isolated rat heart. In the control group, infarct size was 31±5 %, while perfusion of GSE (1, 10, and 100 μg/ml) reduced it to 12±3 (P<0.05), 16±6 (P<0.05) and 2±1 % (P<0.01), respectively. The extract (1 μg/ml) caused significant reduction (P<0.05) in the number, duration and incidence of ischemic ventricular tachycardia (VT). At the reperfusion phase, low concentrations of GSE (especially 1 μg/ml) showed the same effects as well as significant reduction (P<0.05) in the number of ventricular ectopic beats (VEBs). Results of this study showed cardioprotective effects of GSE against I/R injuries by reduction of infarct size and arrhythmias. Maybe, the presence of proanthocyanidin (as free radical scavenging agent) and reduction of intracellular calcium ions may involve in these protective effects.

The purpose of this research, is the preparation of Dithiocarbamate - Zn(II) Complexes and studies on their antibacterial properties in the different concentrations, against the pathogenic bacteria. A series of eight dithiocarbamate as sodium salts of formula R-NHCSSNa and LNa (where R is methyl-, ethyl-, propyl-, nonyland L is diphenyl-, piperidine- and morpholine) and piperazine-bis (dithiocarbamate) sodium salts were prepared by reaction between corresponding amine, CS2 and NaOH. Also, a series of eight complexes have been synthesized through reaction between each of the above eight dithiocarbamate ligands and Zn(NO3 2.6H2O. After the recognation of all compounds and test on their purity, all compounds were assayed for their antibacterial on the Eight Samples of Common Pathogenic Bacteria using, Paper Disk Diffusion method. Standard drugs such as Amoxicillin and Chloramphenicol were used for comparison purpose. Two variables as the length of hydrocarbon chain and the structure of the used amine in ligands and complexes caused different interactions toward microbes. Surveys on the complexes and comparision of their antibacterial properties showed their different effects on different types of bacteria which indicated the role of R groups in the structure. Comparison of the results with those of Amoxicillin and Chloramphenicol showed that the antibacterial activity of Zn dithiocarbamates complexes is better than the corresponding ligands. Among the tested Zn(II) dithiocarbamate complexes, Bis (nonyldithiocarbamato) zinc (II), Bis (piperidinedithiocarbamato) zinc (II) and Bis (morpholinedithiocarbamato) zinc (II) showed the most favorable antibacterial activity against E.coli, Y.entroculitica and P.mirabilis.

During recent years, increasing side effects for syntactic drugs have been motivated by more researchers for finding new compounds of the plant with antifungal activity. Dried fruits extract of Silybum marianum contain flavonoid compounds and until now, no studies have been conducted on the antifungal activates of methanolic extract of this plant. In this study, inhibitory potential of S. marianum methanolic extract on dermatophytes and saprophytes fungi was investigated in vitro compare to clotrimazol. Antifungal activities of S. marianum seeds extract were evaluated against pathogens (Trichophyton mentagrophytes, Epidermaphyton folocosom, Microsporum canis) and saprophytes (Aspergillus niger, Candida albicans) fungi with different methods such as, disc diffusion (60, 30, 15, 7.5, 3.2 and 1.6 mg extract per disc), pour plate and broth (50, 25,12.5, 6.2, 3.1, 1.5 mg ml-1 extract in medium). Concentration of cloterimazol as a control was 10 μg ml-1. Our results showed that, S. marianum seeds extract prevents the growth of dermatophytes more than saprophytes fungi. The best inhibitory effects of extract (6.2 mg ml-1) in Microsporum canis and Epidermaphyton folocosom cultures were achieved by porplate and broth methods that were similar to our results with 10 μg ml-1 cloterimazol. No inhibitory effects were observed in Aspergillus niger and Candida albicans cultures. With attention to our finding, components of the Silybum marianum extract have antifungal effects on the growth of dermatophytes.

Azithromycin is a new macrolide antibiotic with better activity against gram negative bacteria compared to Erythromycin. The purpose of this research was to prepare azithromycin nanosuspension using Poly (lactic-co-glycolic acid) or Eudragit RS 100 polymer and compare the effectiveness of nanosuspensions with drug solutions. Azithromycin nanosuspension was prepared by Modified Quasi Emulsion Solvent Diffusion (MQESD) method. Drug and polymer were dissolved in a water miscible solvent such as aceton. The resulting solution was added to aqueous phase containing two percent of PVA 95000, under homogenization. Nanosuspensions were obtained by migration of solvent from inner to aqueous phase. The microbial culture method was used to compare the effectiveness of nanosuspensions with drug solution. Staphylococcus aureus ATCC 6538 was used in this study. The inhibition zone diameter of azithromycin was determined by diffusion method in agar medium. The obtained inhibition zone diameters for nanosuspensions were compared to those of azithromycin solution. The values pertaining toinhibition zone diameters of nanosuspensions in comparison with those of drug solution were significantly higher, that indicating improved antibacterial activity of the developed formulations (P<0.01). The increased potency of formulated nanosuspensions is perhaps related to some physicochemical properties of nanosuspensions like modified surface characteristics, increased drug adsorption and uptake as well as lower drug degradation. Our results indicate that the potency of nanosuspensions is much more than that of drug solution in the same concentration.

Sustaining diltiazem hydrochloride decreases its frequency of daily dosage, side effects and enhances patient compliance. In order to control the release of diltiazem, the effect of sodium alginate, Na Alg., chain length as well as Al3+ and Ca2+ on the drug release was studied. Matrices with various amounts of Na Alg. containing 120mg drug with different amounts of Al3+ and Ca2+ were prepared and the drug release was measured in distilled water using USP II dissolution tester. The amount of dissolved drug was assayed spectrophotometrically. The release data of various matrices was fitted to some kinetic models (Higuchi, Peppas and Weibull). Various amounts of Na Alg. had different effects on drug release. The most sustained formulations (without cations) were matrices containing 100 mg Na Alg. in both 250 and 3500 grade. The percent of drug dissolved in 240 min for matrices containing 100mg alginate 250 cps and 3500 cps were 83.4 and 59.8, respectively. Due to the ability of Al3+ to crosslink with anionic sites of Na Alg, it may sustain the drug release. Although the addition of Al3+ up to 0.25 meq, sustained the drug release, but the amounts more than 0.25 meq increased the release rate. The release pattern of matrices containing Ca2+ was almost comparable to one of drug alone. The release of diltiazem from matrices can be controlled at any desired rate applying suitable Na Alg. grade together with proper amount of Al3+.

The medicinal plant of Avicennia marina has been used widely in traditional medicine for treatment of skin disease and rheumatoid in Iran. The present investigation was carried out to study the anticancer effects of different crude extracts of A. marina’s leaves against breast cancer cell line (MDA-MB 231). MDA-MB 231 and L929 healthy cells were separately cultured in RPMI-1640 medium completed with 10% fetal calf serum and penicillin / streptomycin (50 IU/ml and 50 μg/ ml respectively). Collected leaves were dried and powdered, then were soaked in five solvents with different lipophilicity. The cytotoxic effects of different concentration of crude extracts on cultured cells were measured using the MTT assay. Chromosomal DNA was extracted, isolated and resolved using agarose gel electrophoresis. Methanolic extract exerted higher anti-cancer activity on human breast cancer cells compared with other extracts. IC50 of the methanolic extract was measured at 480 μg/ml. Furthermore, the methanol extract induced a significant growth inhibition and apoptosis in a dose-dependent manner on MDA-MB 231 as human cancer cells but there was no significant effect against L929 as normal cells. Methanolic extract showed time dependent growth inhibition effect so that, after 24, 4, and 72 h treatment cell growth was inhibited by 40%, 44%, and 59%, respectively. The present results suggest that valuable cytotoxic components could be isolated from this plant by partitioning methanol crude extract. Further investigations are underway in this regard.

Punica granatum L. (pomegranate) is a widely used plant that has high nutritional value. The aim of this study was to assess the effect of administration of pomegranate peel extract (PPE) on blood glucose in diabetic rats. The hydro alcoholic extract was achieved by maceration method from peel of pomegranate. Six groups of rats received streptozotocin and the blood glucose was determined 8 days later for diabetes mellitus. One group of diabetic rats received glibenclamide and 3 groups received extract at dose 200, 400 and 600 mg/kg irnterapritoneally and one group received the extract at dose 600mg/kg orally; one group was kept as control. The serum insulin was measured by kit. The blood glucose was measured by glucometer at 1, 2, 3 and 24 hours after drug administration. The results showed the pomegranate peel extract had significantly better glucose lowering effect at dose 200 mg/kg (IP) and 600mg/kg orally (p<0.05). Also PPE had significantly regulated insulin at dose 600 mg/kg. This study shows beneficial antidiabetic effect of PPE.

Osmotic drug delivery systems have many advantages over traditional dosage forms including: constant release rate, longer duration of action and higher patient compliance. The aim of this study was the design and formulation of a CPOP system of gliclazide as a model of water-insoluble drugs by using solubility enhancing agent in the core formulation. Central cores were made using simple mixing of ingredients and direct compression technique with concave punches under 150 g/cm2 pressure. Dip coating technique was used for coating of core tablets by a semipermeable membrane and the drug concentrations in the samples were analyzed by UV/visible spectrophotometer. Cellulose acetate was used as semipermeable membrane. Polyethylenglycol 200, 300 and 6000 were used as hydrophilic plasticizers. Diethylphtalate and castor oil were used as hydrophobic plasticizers. Tween 80 and sodium lauryl sulphate (SLS) also used as channeling agent and solubility enhancer respectively. Three comparative parameters including D24h (total amounts of the release after 24 hours), %Devzero (mean deviation percents of the drug release from zero order equation) and RSQzero (RSQ of linear regression of release data) were used for the comparison of the prepared formulations. The best D2 h was seen in formulation containing 30mg SLS (7.5%w/w) in core formulation. Semipermeable membranes containing Tween 80 showed higher mechanical resistance than others. Increasing of SLS from 0 to 30mg (optimum amount) was enhanced D24h and improved kinetic related parameters (%Devzero and RSQzero) significantly. This effect probably aroused from solubilization of the drug in medium by solubility enhancer after exposing of the system to dissolution medium.