DARU, Journal of Pharmaceutical Sciences
Volume:13 Issue: 4, Winter 2005

Lyophilization increases the shelf-life of liposomes by preserving it in a dry form as lyophilized cake to be reconstituted with water immediately prior to administration. Aiming at increasing stability and availability of 5-Fluorouracil liposomal products, 5-Fluorouacil Stable Plurilamellar Vesicles were prepared. Freeze dried liposomal dispersions were prepared with or without cryoprotectants. The cryoprotectants used were glucose, mannitol or trehalose in 1, 2 and 4 grams per gram phospholipids. The results showed that lyophilized cake of liposomes without cryoprotectants was compact and difficult to reconstitute, in comparison with fluffy cakes which reconstituted easily and quickly when using cryoprotectants. The percentage of 5-Fluorouracil retained in liposomes freeze-dried without cryoprotectants was 18.29% ± 0.96% and the percentage of 5-Fluorouracil retained in stable plurilamellar vesicles was 31.22% ± 0.62% using 4 grams trehalose as cryoprotectant per gram of lipid. Physico-chemical and release stability studies showed superior potentials of the lyophilized product after reconstitution in comparison to dispersion product. It may be concluded that all tested sugars have cryoprotectant effects that stabilized liposomes in the freeze dried state, where trehalose offered the most superior cryoprotectant effect for freeze dried 5-fluorouracil liposomes.

In the pharmaceutical industry a continuing need for chiral resolution of drugs for various purposes and in diverse matrices exist. For these reasons, analysts may require a number of different separation systems capable of resolving a given pair of enantiomers. Highly sulfated cyclodextrins (HS-CDs) represent a relatively new class of chiral selectors in capillary electrophoresis (CE). In this investigation the use of HS-CDs as chiral selectors in CE for enantioseparation of tramadol, a highly potent analgesic, as the model drug and the influence of the type of selector and its concentration on enantiomeric resolution were studied. All of the available HSCDs (, and ) could resolve tramadol enantiomers, but HS--CD showed better resolution and a baseline resolution was achieved with this selector even at a concentration as low as 0.5% w/v. Additionally, effect of the buffer pH on the enantioresolution was studied. At low pH buffers, in which electroosmotic flow is low in CE, the negatively charged selector prevented the cationic tramadol to migrate out of the capillary even after a long analysis time of 60 minutes. However, at higher pH values (pH=7 or more), the electroosmotic flow is high enough to drag drug-selector complex toward the detector and a reasonable of the enantiomers of the drug was achieved.

Oxidative damage to membrane lipid is one of the prime events occurring in aging and other undesirable physiological processes. In this study experiments were performed on liposomes (prepared either from crude erythrocyte phospholipids or purified egg yolk phosphatidylcholine) as models of lipid bilayer portion of biomembranes. The effects of -carotene, and phospholipid composition on peroxidation process, initiated by Fe2+, were studied. It was found that -carotene does not show any noticeable antioxidant effect on the peroxidation process initiated by Fe2+ in liposomes prepared from erythrocyte phosphatides, whereas it effectively suppressed the same process in egg yolk phosphatidylcholine (EYPC). It is concluded that the anti-/pro-oxidant activity of –carotene is also dependent on the membrane lipid composition and this may provide an explanation about the conflicting reports on its role in ordinary or promoted oxidation experiments.

Desmoperssin is the drug of choice for treatment of central diabetes insipidus and most commonly it is used as intranasal spray. In this study, efficacy and side effects of oral desmopressin was compared with the intranasal spray. This study was before -after clinical trial on 14 outpatients (9 F, 5 M, age 14 -50 Y) with central diabetes insipidus who had been treated with intranasal spray of desmopressin previously. Weight, pulse rate and blood pressure (sitting -standing), biochemical profile, serum electrolytes, 24h urine volume, specific gravity of urine and LFT was measured before and after 1 month study. Starting dose for each patient was one oral tablet of DDAVP (0.1 mg) per 8 hours. Paired Samples T-Test was used for data analysis. No clinically significant changes were found as regard to weight, pulse rate, blood pressure, blood chemistry, electrolyte and urinalysis. Single reported adverse effect was headache (43%) in tablet group and dyspnea (7%) in spray group. Both dosage forms were able to control diurnal polyuria and nocturnal polyuria. The antidiuretic dose - equivalence ratio for intranasal to oral desmopressin was 1: 18. Spray was superior in terms of rapid onset of action and duration of antidiuretic action in 100% and 78% of cases (not significant), respectively. Tablets were more available and much more easily consumed as reported by patients, in 86% (P=0.0006). Treatment with tablets offers a good alternative to the intranasal route, especially in patients with chronic rhinitis or common cold and similar conditions.

Centaurea aucheri (DC.) Wagenitz is one of the species of Asteraceae that has not been the subject of many investigations. Different species of this genus have been used in traditional medicine. In this investigation C. aucheri was collected from Khanesorkh of Kerman and the essential oil of the aerial parts of plant was extracted by Clevenger apparatus and analyzed by GC-MS. Identification of the components of oils were based on their retention indices and mass spectra data in comparison with those reported in literatures. The amount of essential oil was 0.16% and 22 substances consisting 80.03% of the composition of the essential oil were identified. The main compounds were caryophyllene oxide (19.44%), β-caryophyllene (14%), Geremacrene-D (13.38%). The essential oil was rich in sesquiterpene oil.

Extracts of the flowering aerial parts of Stachys schtschegleevii Sosn. and S. balansae Boiss. and Kotschy ex Boiss have been used in Iranian folk medicine as remedy for rheumatic and other inflammatory disorders and anti-inflammatory and analgesic effects of some species of Stachys e.g. Stachys inflata have been reported. In this study, the anti-inflammatory and antinociceptive properties of total methanolic extracts of the flowering aerial parts of two Stachys species in rat were investigated by carrageenan-induced paw edema and formalin test. Intraperitoneal injection of the extracts, 60 min before induction of inflammation, resulted in inhibition of carrageenan-induced rat paw edema in dose dependant manner (doses 50, 100 and 200 mg/kg). In the formalin test, the extract (50, 100 and 200 mg/kg) had low effect in the first phase (0–5 min) of the formalin-induced pain, but all three doses showed analgesic and anti nociception effects significantly. In conclusion the methanolic extracts of Stachys schtschegleevii and Stachys balansae have analgesic and anti-inflammatory effects in formalin test and carrageenan-induced paw edema.

On the basis of reports that mesenchymal stem cells (MSCs) can be isolated from the placenta/umbilical cord stroma, the present study was undertaken to isolate and characterize MSCs from the human umbilical cord veins. In this investigation, a cell population was isolated which was derived from the endothelium/subendothelium layers of 20 umbilical cord veins obtained from term deliveries using a solution of 0.1% collagenase type IV. Results suggest that these cells possess morphological, immunophenotypical and cell differentiation capacities similar to the bone marrow-derived mesenchymal stem cells (MSCs). The isolated cell population has fibroblastoid morphology which upon proper stimulation gives rise to adipocytes, osteocytes and chondrocytes in culture. Immunophenotypically, this cell population is positive for CD54, CD29, CD73, CD49e, CD166, CD105, CD13, and CD44 markers and alpha-smooth muscle actin and negative for CD31, CD45, CD49d, and CD34 markers, von Willebrand factor (vWF) and smooth muscle myosin (MySM). Altogether, these findings indicate that umbilical cord obtained from term deliveries is an important source of MSCs which could have an important application in cell therapy protocols.

From the aerial parts of Satureja macrantha C. A. Mey, one monoterpene (1), two triterpenoids (2,3) and one sesquiterpene (4) were isolated. Their structures were determined to be thymol (1), oleanolic acid (2), ursolic acid (3) and caryophyllene oxide (4), by using 1H and 13C-NMR, FTIR and EIMS spectra. Brine shrimp cytotoxicity effects of the crude extracts and isolated compounds were examined. Among them compounds 1 (612 μM), 2 (17 μM) and 3 (29 μM) were effective against Artemia salina larva.