DARU, Journal of Pharmaceutical Sciences
Volume:11 Issue: 3, Autumn 2003

Abstract: Majority of the currently available anticancer drugs are designed to have selective toxicity to rapidly dividing cells. Among these agents the focus of many studies are compounds obtained from natural products with high therapeutic index. In this study the cytotoxicity of HESA-A, a marine compound, on cancer and normal cells was evaluated. HESA-A was prepared in normal saline as a stock solution (0.8 mg/ml, pH=7.4), sterilized and further diluted to final concentrations of 0.4, 0.2, 0.1 and 0.05 mg/ml. Cells (MDA-MB-468, Hep-2, Hela as cancer cells; L929 and McCoy as normal cells) were grown in completed RPMI 1640 and seeded in 96 well micro plates at a concentration of 1-5 ´ 104 cells/ml. After incubation for 24 h, different concentrations of HESA-A were added and cells were further incubated for 72 h. Using MTT assay, percent cell survival was determined by ELISA at 540 nm. Doxorubicin was used as a positive control (20 mg /ml). HESA-A (0.4 mg/ml) reduced the number of viable MDA-MB-468 and Hela cells to less than 50%. For Hep-2 cells the IC50 was 0.8 mg/ml. In normal cells IC50 could not be obtained at any given concentrations. These results suggest that HESA-A in therapeutic doses and in a concentration dependent manner inhibits the growth of cancer cells more selectively than normal cells.

Abstract: Encapsulation of drugs into multivesicular liposomes (Depofoam) offers a novel approach to sustained release drug delivery. Depofoam –encapsulation has been shown to result in sustained-release lasting over several days to weeks after non-vascular administration. In this paper we describe encapsulation of desferrioxamine in a multivesicular (MVL) depot –delivery system. The Depofoam particles were characterized by their morphology, particle size and capture volumes. The effects of various concentrations of components and two manufacturing methods on capture volumes of these particles were studied. The light micrograph showed that particles were smooth and multivesicular without any debris. The particle size of these liposomes were between 15-35 μm with capture volumes about 27%. The results show that the concentration of triolein in lipid combination and lysine in the second aqueous solution have significant effects on the captured volume.The in vitro studies in 0.9% NaCl at 37 ºC showed that the multivesicular liposomes released desferrioxamine slowly over several days, and 57% desferrioxamine was released in 9 days.

Abstract: This study was designed to assess pharmacokinetic parameters and pattern of pharmacodynamic effects (heart rate and blood pressure) of 100 mg Atenolol tablets in comparison with those of 100 mg Tenormin tablets as reference. A double blind cross over study was carried out among 12 healthy male subjects. A HPLC system using RP-C18 column and fluorescence detector was used to assess atenolol in plasma. Heart rate and blood pressure were measured by the trained clinic staff. Peak levels were observed about 2.97h for Atenolol and 3.73h for Tenormin after oral dosing. Cmax values for both formulations were about 0.49 mg/ml. AUC0-24 was about 4.89 mg.h/ml for the test and 5.31 mg.h/ml for the reference group. Atenolol given orally caused a significant reduction in heart rate, systolic and diastolic blood pressure after administration of two formulations (P<0.05). It is concluded that two formulations are not significantly different in terms of pharmacodynamic and pharmacokinetic parameters which were studied.

Abstract: Since digoxin possesses a narrow therapeutic index and shows a large interpatient pharmacokinetic variability, serum digoxin monitoring is a suitable guideline for optimization of digoxin therapy. However, digoxin concentration monitoring is not always accessible; and as result sometimes in order to prevent digoxin toxicity a drug holiday is performed (the drug is off for 1 or 2 days a week). In this investigation a prospective cohort study was designed to evaluate drug regimen. One hundred and twenty three inpatients receiving digoxin for heart failure or atrial were included in this study. In the group with a drug holiday regimen, 3 samples of serum were taken from each patient. (Preholiday trough, 6-8 hrs after the last dose in steady state, post holiday trough). In other groups 2 samples were collected (trough and 6-8 hrs after the last dose in steady state) and samples were assayed by radioimmunoassay. The results showed that 73.33% of patients receiving 0.125 mg/day had a level less than 0.8 ng/ml (sub therapeutic). While most patients had preholiday concentration within therapeutic range (0.8-2 ng/ml), due to the concentration fluctuation, clinical ineffectiveness of this drug regimen is questionable. In patients with 0.25 mg/day regimen, 62.5% of had therapeutic level and an appropriate clinical response. While a population pharmacokinetic analysis must be designed for a proper decision about the dosage adjustment in patients of this study in future, it seems that 1 tablet/day regimen is preferred.

Abstract: The ability of polyvinyl pyrrolidone (PVP) and bovine serum albumin (BSA) in inhibition of the crystal growth inssuspensions containing Acetaminophen as a model drug was evaluated. For this purpose sedimentation volume, resuspendability, cake formation, particle size distribution, volume surface diameter (dvs), and crystal growth after freeze-thaw cycling of the several suspensions were evaluated. ANOVA followed by Tukey test was used to determine significant differences (P<0.05). PVP in comparison with BSA showed a better crystal growth inhibition and at concentrations of 50-100 mg/100 ml inhibited crystal growth over 150 days. The combination of PVP and BSA showed an inhibition of acetaminophen crystal growth after 45 and 150 days respectively. The combination of PVP (50 mg/100 ml) and BSA (80 mg/100 ml) showed interesting results regarding sedimentation volume, resuspendability, prevention of cake formation, and crystal growth inhibition; and offer new perspectives in the preparation of suspensions.

Abstract: The absolute glomerular volume and total glomerular number as well as renal volume in diabetic rats following administration of different doses of Stereptozotocin (STZ) have been estimated by using unbiased stereological methods. 30 male Wistar rats were randomly divided into 5 groups. Diabetes were induced by IP injection of 15mg/kg, 45mg/kg and 90 mg/kg of STZ. Fifty six days after IP injection, animals were anesthetized by ketamine hydrochloride, the kidneys were excised and fixed in modified Lilli´s solution. After tissue processing and staining, stereological methods used to estimate volume of different zones of kidney, absolute glomerular volume and total glomerular number. This investigation revealed that increment of cortical tissue volume in all groups and increase in medullary volume only in the group 90 mg/kg of STZ (p<0.01) were administered. Glomerular volume was increased significantly in all groups (p<0.01) but no changes in total glomerular number were detected (p>0.05). Animal weight also showed significant changes in 45 mg and 90 mg groups in comparison with the control group (p<0.01). This study showed that at least administration of more STZ in short period might have more effect and causes more imbalances in cells turnover. The results of this study were in accordance with other qualitative and quantitative surveys. Moreover, it was suggested that in the early stages of the induced diabetes mellitus by STZ, the inducer has different effects and more doses may cause more induction and effects on kidneys.

Abstract: This study was designed for evaluation of epiphyseal plate histological changes of femur bones in osteopetrotic op/op mice.In this study 5 osteopetrotic op/op mice which were purchased from the commercial source were used.The animals were killed by overdose of chloroform and their femur bones were extracted. The bones were fixed in 10% formaldehyde and decalcified by HCl (0.6N), and routine histological processing were performed. The sections were stained by H&E methods and studied by conventional light microscopy. The results showed that, proliferative zone (PZ) and especially hypertrophic zone (HZ) were much thickened. In the ossification zone, trabecular bones were irregular and atypical osteoblast cells were observed. The osteoclast cells were not attached to trabecular bones. The bone marrow cavity was restricted and bone marrow cells were poor and scattered. Findings of the present investigation are similar to those reported about epiphyseal plate in osteosclerotic (OC) mice in which epiphyseal plate especially hypertrophic zone was thickened and chondrocytes were not substituted for osteoblasts in calcified cartilage area. Also, osteoclast cells had been inactive or absent in OC mice. For prevention of other complication due to the epiphyseal plate changes in new borne, suitable and punctually treatment protocols such as prescription of Macrophage Colony Stimulating-Factor (MCS-F) could be useful.

Abstract: Hydrodistillation of aerial parts of Cymbopogon olivieri (Boiss.) Bar (Andropogonae) yielded 1.7% v/w of the essential oil. By GC and GC/MS twenty-two components, representing 94.80% of the total oil composition were identified. The major constituents were Δ-3 carene (22.46%), piperitone (44.90%) and α-eudesmol (13.33%). The essential oil of Cymbopogon olivieri (Boiss.) Bar showed interesting activity against larvaes of Anophel stephensi (LD50=321. 902 p.p.m.).