فهرست مطالب

Research in Pharmaceutical Sciences - Volume:10 Issue: 6, Dec 2015

Research in Pharmaceutical Sciences
Volume:10 Issue: 6, Dec 2015

  • تاریخ انتشار: 1394/10/30
  • تعداد عناوین: 10
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  • Sheri Ps, Prasanth Vv Pages 466-476
    The objective of the present work was to formulate and evaluate mucoadhesive in situ nasal gels of loratadine. This drug delivery system may overcome the first-pass metabolism and subsequently improve the bioavailability of the drug. A total of 16 formulations of in situ nasal gels were prepared using different polymeric ratios of hydroxypropyl methylcellulose (HPMC K-100) and xanthan gum. All formulations had a clear appearance in the sol form, with gelling temperature of the nasal gels ranging between 33.1 ± 0.43 and 34.8 ± 0.82 °C. The gelling time of all the formulations varied from 4.0 ± 0.21 to 11.3 ± 0.22 s; the drug content was >95%. The pH of the formulations ranged between 5.6 ± 0.004 and 6.0 ± 0.003, i.e. no mucosal irritation is expected as the pH was in the acceptable range. Mucoadhesive strength was adequate (3010.89 ± 1.21-6678.89 ± 0.45 dyne/cm2) to provide prolonged adhesion. In vitro drug release studies showed that the prepared formulations could release the drug for up to 10 h with all of them following Higuchi kinetics. The accelerated stability studies indicated that the gels were stable over the six months test period. The DSC and XRD analysis revealed that there was no drug-polymer interaction. From these findings it can be concluded that in situ nasal gels may be potential drug delivery systems for loratadine to overcome first-pass metabolism and thereby to improve the bioavailability.
    Keywords: In situ nasal gel, Loratadine, Controlled drug release, Gelling temperature, Accelerated stability studies
  • V. Hajhashemi *, A. Safaei Pages 477-484
    The aim of the present study was to evaluate hypnotic effect of Coriandrum sativum, Ziziphus jujuba, Lavandula angustifolia and Melissa officinalis hydroalcoholic extracts in mice to select the most effective ones for a combination formula. Three doses of the extracts (250, 500 and 1000 mg/kg of C. sativum and Z. jujuba and 200, 400 and 800 mg/kg of L. angustifolia and M. officinalis) were orally administered to male Swiss mice (20-25 g) and one hour later pentobarbital (50 mg/kg, i.p.) was injected to induce sleep. Onset of sleep and its duration were measured and compared. Control animals and reference group received vehicle (10 ml/kg, p.o.) and diazepam (3 mg/kg, i.p.), respectively. C. sativum and Z. jujuba failed to change sleep parameters. L. angustifolia at doses of 200, 400 and 800 mg/kg shortened sleep onset by 7.6%, 50% and 51.5% and prolonged sleep duration by 9.9%, 43.1% and 80.2%, respectively. Compared with control group the same doses of M. officinalis also decreased sleep onset by 24.7%, 27.5% and 51.2% and prolonged sleep duration by 37.9%, 68.7% and 131.7% respectively. Combinations of L. angustifolia and M. officinalis extracts showed additive effect and it is suggested that a preparation containing both extracts may be useful for insomnia.
    Keywords: Hypnotic, Sleep, Coriandrum sativum, Ziziphus jujuba, Lavandula angustifolia, Melissa officinalis, Mice
  • S. Soltani, F. Mokarian, M. Panjehpour* Pages 485-496
    Breast cancer is the most common cancer in women worldwide. Breast cancer in one third of all patients will go on to metastasis, which is the main cause of mortality in cancer cases. Tumor cells detach from primary tumor and enter into the circulation as circulating tumor cells (CTCs) which can form metastatic lesions. In this study, the expression of CK-19 gene in blood samples of metastatic breast cancer women was investigated and compared to control group. Twenty one patients with metastatic breast cancer and 20 healthy female volunteers enrolled in this study. For every patient and healthy donor 10 ml peripheral blood was collected. Peripheral blood mononuclear cells were isolated by gradient density centrifugation using Ficoll Hypaque. CK-19 gene expression was evaluated using SYBR green-based real-time quantitative polymerase chain reaction assays. The relative expression level of CK-19 was calculated using the 2−ΔΔCt analysis method. The mean of CK-19 expression was increased in metastatic breast cancer when compared to those of normal women (1.50 fold). 38.1% of the metastatic breast cancer patients showed CK-19 mRNA-detectable CTCs in their blood samples. There was no statistically significant difference between the relative expression level of CK-19 and the patient’s clinicopathological characteristics. According to our knowledge, no study for determining CTC biomarkers in Iranian breast cancer women patients has yet been established. Our results suggest that the CK-19 mRNA expression investigation may be useful for monitoring CTCs in the blood of metastatic breast cancer patients, predicting early metastatic relapse or monitoring of anti-metastasis treatments.
    Keywords: Circulating tumor cells, Breast cancer, CK, 19, Metastasis
  • H. Sadraei*, Ghr Asghari, M. Motaqedi Pages 497-503
    Genus Peucedanum belongs to the subfamily of Apioideae (Umbelliferae family) and is reported to have many medicinal properties. Several spiecis of Peucedum reported to have antispasmodic activity. Peucedanum pastinacifolium species grows in Iran. However, so far there is no report on its antispasmodic activity. The objective of this research was to investigate antispasmodic activities of P. pastinacifolium extract using in vitro isolated tissue techniques. Hydroalcoholic and hexanoic extracts were prepared by perculation method from aerial part of P. pastinacifolium. A portion of rat isolated ileum was suspended under 1g tension in Tyrode’s solution at 37 °C and gassed with O2. Effects of extracts of P. pastinacifolium were studied on ileum contractions induced by KCl (80 mM), acetylcholine (ACh, 250 µM) and electrical field stimulation (EFS). The hydroalcoholic extract P. pastinacifolium concentration dependently inhibited the response to KCl (IC50=220 ± 30 mg/ml), ACh (IC50=175 ± 15 mg/ml) and EFS (IC50=95 ± 15 mg/ml). The hexanoic extract of P. pastinacifolium also had inhibitory effect on ileum contraction induced by KCl (IC50=16 ± 2 mg/ml), ACh (IC50=30 ± 5 mg/ml) or EFS (IC50=11 ± 4 mg/ml). From these experiments it was concluded that both hydroalcoholic and hexanoic extract of P. pastinacifolium contain substances which have antispasmodic activities but these substances are mainly concentrated in the hexanoic extract.
    Keywords: Peucedanum pastinacifolium, Ileum, Antispasmodic
  • M. Rostami, L. Rafiee, F. Hassanzadeh*, Ar Dadrass, Gha Khodarahmi Pages 504-513
    Porphyrins are a ubiquitous large class of naturally occurring macrocyclic compounds with many significant biological representatives comprising heme and chlorophyll. Some novel adaptable methods for the synthesis of free-based porphyrins as promising sensitizers for the use in photo-dynamic therapy by the virtue of their known tumor affinity, low dark cytotoxicity, and easy synthesis in good to high yields have already been discussed. In the present study, two new porphyrins including TAPFA, as a novel folic acid targeted porphyrin sensitizer, and TAP-Schiff base, as a novel sensitizer with better light absorption, were prepared for the first time and their structures were confirmed by 1H NMR, 13C NMR, FT-IR and UV-Vis spectroscopy as well as CHNS analysis . The compounds were metalized with Zn(II) and Fe(II) metal ions to study how the metal ions can improve the light absorption wavelength and their water solubility. The structures of metalized compounds were also confirmed by FT-IR and UV-Vis spectroscopy.
    Keywords: Porphyrins, Metalloporphyrins, Photo, dynamic therapy (PDT), Two, photon absorption (TPA)
  • Gh Latifi, A. Ghannadi, M. Minaiyan* Pages 514-522
    Rosa damascena is a small plant belonging to Rosaceae family which has been used for the treatment of some inflammatory diseases and digestive disorders in the Iranian folk medicine. This study was performed to investigate the effect of R. damascena hydroalcoholic extract (RDHE) and R. damascena volatile oil (RDVO) on ulcerative colitis induced by acetic acid in rats. Different doses of RDHE (250, 500, 1000 mg/kg) and RDVO (100, 200, 400 µl/kg) were given orally (p.o.) and doses of RDHE (125, 250, 500 mg/kg) were administrated intraperitoneally (i.p.) to the male Wistar rats (n=6) 2 h before induction of colitis which continued daily for 4 successive days. Prednisolone (4 mg/kg p.o.) and dexamethasone (1 mg/kg i.p.) were used in the reference groups. Weight/length ratios of wet colon were measured and the tissues were assessed macroscopically, histopathologically, and biochemically via measuring the myeloperoxidase (MPO) activity. Oral RDHE at all doses examined, and the lowest dose of RDVO given p.o. or RDHE administered i.p. reduced all indices of colitis measured in different assays as well as the MPO activity. These results provide encouraging support for the use of hydroalcoholic extract of R. damascena in relieving alimentary inflammatory conditions and reinforce the use of this plant to develop new agents for treating ulcerative colitis.
    Keywords: Rosa damascena, Inflammation, Colitis
  • A. Ghasemi *, M. Mohtashami, S. Sotoudeh Sheijani, K. Aliakbari Pages 523-534
    Alpha-1antitrypsin (A1AT) deficiency, an inherited disorder, has been shown to be the cause of lung diseases such as emphysema and chronic obstructive pulmonary disease. One of the treatment strategies to provide appropriate and adequate concentrations of A1AT in the lungsis the application of nanoparticles (NPs) in pulmonary drug delivery. In the current study, biocompatible nanohydrogels were prepared using chemically cross-linked chitosan with ginepin, a natural cross linker reagent, and used as a carrier to deposit A1AT into the lung tissue. Colloidal and monodispersed NPs were synthesized through reverse microemulsion. Nanohydrogels were characterized with TEM, LLS, FTIR, ZTEA potential, UV spectrum, and swelling test. Encapsulation efficacy was determined at different concentrations of A1AT using Bradford assay. Effect of processing variables such as pH, loading efficiency, and release media components on drug release profile was determined in simulated lung fluids. To evaluate the inhibitory activity of the A1AT after release from NPs, trypsin inhibitory capacity assay was carried out. Results from FTIR and UV spectrum confirmed the development of chitosan cross linkage. Spherical chitosan-genipin NPs were sized from 30-100 nm . NPs exhibited the ability to release 49% of the drug within 12-dayperiodatpH 7. However, there were variations with the drug release profile due to pH variations and loading efficacy. Drug release was higher in pseudo alveolar fluid in comparison with saline solution. These data indicate that application of chitosan nanohydrogels can be a useful tool for sustained release of A1AT in the lung tissue.
    Keywords: Alpha, 1antitrypcin, Chitosan, Genipin, Nanohydrogel, Simulated lung fluids, Drug delivery
  • M. Rabbani *, Se Sajjadi, A. Vaezi Pages 535-543
    Ocimum basilicum belongs to Lamiaceae family and has been used for the treatment of wide range of diseases in traditional medicine in Iranian folk medicine. Due to the progressive need to anti-anxiety medications and because of the similarity between O. basilicum and Salvia officinalis, which has anti-anxiety effects, we decided to investigate the anxiolytic and sedative activity of hydroalcoholic extract and essential oil of O. basilicum in mice by utilizing an elevated plus maze and locomotor activity meter. The chemical composition of the plant essential oil was also determined. The essential oil and hydroalcoholic extract of this plant were administered intraperitoneally to male Syrian mice at various doses (100, 150 and 200 mg/kg of hydroalcoholic extract and 200 mg/kg of essential oil) 30 min before starting the experiment. The amount of hydroalcoholic extract was 18.6% w/w and the essential oil was 0.34% v/w. The major components of the essential oil were methyl chavicol (42.8%), geranial (13.0%), neral (12.2%) and β-caryophyllene (7.2%). HE at 150 and 200 mg/kg and EO at 200 mg/kg significantly increased the time passed in open arms in comparison to control group. This finding was not significant for the dose of 100 mg/kg of the extract. None of the dosages had significant effect on the number of entrance to the open arms. Moreover, both the hydroalcoholic extract and the essential oil decreased the locomotion of mice in comparison to the control group. This study shows the anxiolytic and sedative effect of hydroalcoholic extract and essential oil of O. basilicum. The anti-anxiety and sedative effect of essential oil was higher than the hydroalcoholic extract with the same doses. These effects could be due to the phenol components of O. basilicum.
    Keywords: Ocimum basilicum, Anti, anxiety, Sedative, Extract, Essential oil
  • H. Hassanian, Moghaddam*, F. Farnaghi, M. Rahimi Pages 544-552
    We aimed to determine the clinical manifestations of tramadol intoxication in children and to find its potential poor prognostic factors. In a retrospective study, from 1363 cases of admitted pediatric poisoning, all tramadol-exposed hospitalized patients younger than 12 years were included in the study. They were hospitalized between March 2010 and April 2012 to the only referral hospital for pediatric poisoned patients in Tehran, Iran. Data including age, weight, gender, ingested dose (determined by history), pupil size, seizure, apnea, treatment interventions, and laboratory results was collected using chart review of the hospitalized intoxicated children. Twenty children with a mean age of 3.7 ± 2.9 years were identified amongst children during this 26-month period of whom, 14 (70%) had a decreased level of consciousness, 3 (15%) experienced apnea, and four (20%) had nausea and vomiting. Witnessed seizure did not occur in any of these patients. All patients were referred to hospital within 10.5 h of the exposure. The mean ingested dose was 9.6 ± 5.5 mg/kg. There was no significant relation between apnea and the estimated toxic dose. Apnea was more common in children who had presented with respiratory acidosis (Relative risk = 3.8, 95% CI = 1.6, 8.7, P = 0.043). All patients survived. Patients with apnea were managed conservatively by naloxone and recovered without need for intubation. Respiratory depression might occur at doses just above the therapeutic dose. We recommend an observation time of 12 h for all asymptomatic children who have ingested any dose greater than the therapeutic one.
    Keywords: Tramadol, Intoxication, Overdose, Intensive care units, Pediatric, Apnea
  • L. Haddad, V. Babaeipour, Mr Mofid* Pages 553-561
    The isolation of the target protein from inclusion bodies (IBs) is a preliminary step to increase protein titer and to maintain its biological activity. In the present study, the effects of various cell lysis methods and the expression temperature was investigated on the improvement of the subsequent purification steps of mecasermin produced in IB. We also investigated the solubilization profile of the top-notch IB in 6 M guanidine hydrochloride (Gdn-HCl) and 8 M urea at different pH ranges. Mecasermin was expressed at various temperatures (25, 28, 30, and 37 °C) and the Escherichia coli cells were lysed by different cell lysis methods. The purity and quality of harvested IBs was evaluated with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Finally, mecasermin was refolded and purified using gel filtration chromatography. The profile of SDS-PAGE analysis showed higher quality and purity after application of sonication coupled with lysozyme pretreatment for expressed mecasermin at 37 °C. Besides, from dithiothreitol application in washing step, we achieved a manifold enriched secondary IB for further purification of mecasermin. Mecasermin exhibited optimized solubility in 6 M Gdn-HCl at pH of 5.4. The findings of this study indicate an important role for cell disruption techniques to efficient purification of mecasermin. The study presents the most efficient techniques for improvement of downstream purification of mecasermin.
    Keywords: Cell disruption, Inclusion body purification, Mecasermin, Strong chaotrope