{"title":"Discovery of Novel Peptidomimetics for Brain-Derived Neurotrophic Factor using Phage Display Technology","authors":"Fatemeh Nafian, M. Rasaee, S. Yazdani, Z. Soheili","doi":"10.22034/IJPS.2018.37554","DOIUrl":"https://doi.org/10.22034/IJPS.2018.37554","url":null,"abstract":"Brain-Derived Neurotrophic Factor (BDNF) is a neuroprotectant candidate for neurodegenerative diseases. However, there are several clinical concerns about its therapeutic applications. In the current study, we selected BDNF-mimicking small peptides from phage-displayed peptide library as alternative molecules to the clinical challenges. The peptide library was screened against BDNF receptor (Neurotrophic Tyrosine Kinase Receptor Type 2, NTRK2) and evaluated by ELISA. Polyclonal phage ELISA indicated that target populations were enriched round by round and the panning process was truly effective. The results of monoclonal phage-ELISA showed that all clones had principally bound to NTRK2 but fifteen best clones were sequenced, which twelve of them have SGVYKVAYDWQH (peptide 1) sequence, two pairs were GLHTSATNLYLH (peptide 2), and TVLSHPSTATLI (peptide 3) and one sequence was QQRPYVQDLRLI (peptide 4). Alignment of these peptides and BDNF sequence showed that the resulting peptides conformationally mimicked loop 2 (E40-KVPVSKGQLK-Q51) of BDNF. This region of BDNF is responsible for specific receptor binding and biological activity. According to the similarity of these peptides with BDNF, they could be considered as novel peptidomimetics with therapeutic properties. In addition, modeled peptides were submitted to Protein Model Data Base (peptides 1, 2, 3 and 4 as PMDB ID: PM0081104, PM0081105, PM0081106, PM0081107, respectively).","PeriodicalId":14582,"journal":{"name":"Iranian Journal of Pharmaceutical Sciences","volume":"14 1","pages":"9-20"},"PeriodicalIF":0.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41577291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Farimah Rahimi, H. Rasekh, F. Peiravian, E. Abbasian
{"title":"Using Discrete Choice Experiment to Determine Willingness to Pay for Medicine Interferon-Beta by Multiple Sclerosis Patients","authors":"Farimah Rahimi, H. Rasekh, F. Peiravian, E. Abbasian","doi":"10.22034/IJPS.2018.37550","DOIUrl":"https://doi.org/10.22034/IJPS.2018.37550","url":null,"abstract":"This study explores the effects of Interferon-β characteristics such as country of origin, injection frequency and method, monthly cost, efficacy, and side effects on multiple-sclerosis patients’ willingness to pay. For this purpose, MS patients with a history of using Interferon-β were studied from the three major Isfahan MS centers. Choice sets were designed with a combination of attributes and levels. The variables in this experiment included interferon-β with different levels assigned to each of its attribute. Patient preferences and willingness to pay were calculated through Discreet Choice Experiment. The statistical population consisted of 358 patients deemed eligible for the study. They responded to the questionnaire and took part in interviews. Results showed that the highest willingness-to-pay value of US$ 223 as determined by MS patients belonged to a change of efficacy from moderate to high. Side-effects and ease of use ranked next among patient preferences. Country of origin recorded the lowest value of the willingness-to-pay parameter. Evaluation of MS patients' preferences as reflected in their willingness to pay plays an important role in patient’s adherence to treatment to achieve more effective results. Due to the variety of drugs in this category, it is necessary to identify and prioritize those features that are of interest to patients and that increase their utility relative to IFN-β drugs.","PeriodicalId":14582,"journal":{"name":"Iranian Journal of Pharmaceutical Sciences","volume":"14 1","pages":"71-78"},"PeriodicalIF":0.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48457719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanobody as a new generation of functional proteins","authors":"Zahra Ebrahimi, R. Arezumand, A. Ramazani","doi":"10.22034/IJPS.2018.35933","DOIUrl":"https://doi.org/10.22034/IJPS.2018.35933","url":null,"abstract":"Nanobody (Nb) or VHH is the smallest binding domain of camelid heavy chain antibody (HcAb). Light chains of HcAb naturally removed and because of some evolutionary changes, Nbs have unique properties rather than conventional antibodies. The size of Nb is about one-tenth (0.1) of whole antibodies and this size improved some problems of four chains antibodies such as high yield of expression in prokaryotic systems and penetration to tissues. Some other characterizes of Nb like close homology to human VH, high stability in the extended range of pH and temperature, the capability to the identification of unusual epitope is very attractive for research and development of new Nb candidates for diagnosis, research, and therapeutic applications. Discovery of Nb almost coincided with advancement in phage display technology that was used along with Hybridoma technology in monoclonal antibody development. Currently, many of research groups focused on high-quality Nbs development against different targets especially in cancers and fortunately there are many of Nbs in clinical trial stages for use in extended ranges of diseases such as cancers, autoimmune and inflammatory diseases and infectious diseases. Recently two of them were approved for clinical use. Big companies like Ablynx and Merck have been invested in this field and in future, further drugs base Nbs were approved in different areas of health science. In this review, we focused on production, features, and clinical application of Nbs and will be noted to Nbs in clinical trials.","PeriodicalId":14582,"journal":{"name":"Iranian Journal of Pharmaceutical Sciences","volume":"14 1","pages":"91-106"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43145104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shirin Mofavvaz, M. Sohrabi, Shiva Sahebi Farhad, Alireza Nezamzadeh‐Ejhieh
{"title":"Least-squares support vector machine and its application in the simultaneous quantitative spectrophotometric determination of pharmaceutical ternary mixture","authors":"Shirin Mofavvaz, M. Sohrabi, Shiva Sahebi Farhad, Alireza Nezamzadeh‐Ejhieh","doi":"10.22034/IJPS.2018.35925","DOIUrl":"https://doi.org/10.22034/IJPS.2018.35925","url":null,"abstract":"This paper proposes the least-squares support vector machine (LS-SVM) as an intelligent method applied on absorption spectra for the simultaneous determination of paracetamol (PCT), caffeine (CAF) and ibuprofen (IB) in Novafen. The signal to noise ratio (S/N) increased. Also, In the LS - SVM model, Kernel parameter (σ2) and capacity factor (C) were optimized. Excellent prediction was shown using LS-SVM, with lower root mean square error (RMSE) and relative standard deviation (RSD). In addition, Regression coefficient (R2), correlation coefficient (r) and mean recovery (%) of this method obtained for PCT, CAF and IB. LS- SVM / spectrophotometry method is reliable for simultaneous quantitative analysis of components in commercial samples. The results obtained from analyzing the real sample by the proposed method compared to the high- performance liquid chromatography (HPLC) as a reference method. One-way analysis of variance (ANOVA) test at 95% confidence level used and results showed that there was no significant difference between suggested and reference methods.","PeriodicalId":14582,"journal":{"name":"Iranian Journal of Pharmaceutical Sciences","volume":"14 1","pages":"25-36"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43098887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insulinomimetic Effect of Citrullus Colocynthis Roots in STZ Challenged Rat Model","authors":"Sireesha Kalva, N. Fatima, R. Nerella, S. Samreen","doi":"10.22034/IJPS.2018.65235.1324","DOIUrl":"https://doi.org/10.22034/IJPS.2018.65235.1324","url":null,"abstract":"Abstract Diabetes mellitus is a metabolic disease characterized by hyperglycemia resulting from either defect in insulin secretion, insulin action, or both. Postprandial hyperglycemia is a prime characteristic of diabetes mellitus and has been a focus in the therapy for diabetes. One of the therapeutic approaches which involve decreasing hyperglycemia aims at lowering blood glucose by decreasing insulin resistance, raising insulin sensitivity at the tissues and inhibiting the carbohydrate absorbance in the intestine. Plants contain different chemical constituents with potential for insulin mimetic action, decrease in insulin resistance and of α-amylase inhibitory activity may be used as therapeutic agents in the treatment of diabetes mellitus. The present study investigates the hypoglycemic activity and insulinomimetic action of aqueous and ethanolic extracts of Citrullus colocynthis by invitro α-amylase enzyme inhibition and by histopathological studies in streptozotocin (STZ) induced diabetic rats. Male Wistar rats weighing about 180- 250g were taken and divided into fifteen groups. Diabetes was induced by giving streptozotocin (STZ) (30-50mg/kg) intraperitoneally. Rats that showed blood glucose levels > 250mg/dl were selected for the study. Metformin (45mg/kg) was given as standard oral hypoglycemic agent. The aqueous and ethanolic extracts of Citrullus colocynthis (AECC and EECC) at 100mg/kg, 200mg/kg and 300mg/kg were administered to the normal and diabetic rats. The invitro α – amylase inhibitory activity was done by spectrophotometric method. Blood glucose levels were measured by glucose oxidase method. Estimation of glycogen in the lever was carried out with anthrone method. Liver and pancreas were isolated and subjected to histopathological studies. Serum insulin was monitored through chemiluminescence assay. Oral administration of both extracts showed significant inhibition of α-amylase enzyme in-vitro and decrease in blood glucose also. Glycogen and Insulin levels too were found to increase in extract treated groups which attributed for its insulinomimetic activity. The findings revealed that Citrullus colocynthis possess a very strong anti-hyperglycemic potential justifying the use of the drug for the treatment of diabetes mellitus.","PeriodicalId":14582,"journal":{"name":"Iranian Journal of Pharmaceutical Sciences","volume":"14 1","pages":"49-66"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41807611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protective Effects of Pioglitazone against Dextran Sodium Sulphate-Induced Colitis in Rats.","authors":"S. E. Awdan, R. Mostafa","doi":"10.22034/IJPS.2018.35923","DOIUrl":"https://doi.org/10.22034/IJPS.2018.35923","url":null,"abstract":"The aim of the present study is to investigate the preventive effect of pioglitazone on colitis induced with dextran sulfate sodium (DSS) in rats. Twenty-four male Sprague-Dawley rats weighing 180-200 g were randomized into four groups. Rats of the 1st group received only saline and served as normal group. Colitis was induced in the remaining 3 groups by 1.5% DSS administered in drinking water for 8 days. Group 2 received only saline p.o. for 30 days and served as DSS control group. Groups 3 and 4 received pioglitazone (PIO; 10 mg/kg/day, p.o.) and sulfasalazine (SUL; 300 mg/kg) respectively for 30 days. All animals were sacrificed 24 h after the last treatment. Serum levels of interleukin-2 (IL-2), interleukin-6 (IL-6) and interleukin-17 (IL-17) were measured. Levels of tumor necrosis factor-α (TNF-α), reduced glutathione (GSH) and malondialdehyde (MDA), were measured in colon tissue. Significant elevation in GSH levels and reduction in MDA and TNF-α levels in colon tissue were observed in pioglitazone and sulfasalazine treated group when compared with the DSS control group. Significant elevation in serum IL-2 and reduction in serum IL-6 and IL-17 were observed when compared with the DSS control group. Pioglitazone reduced DSS-induced colitis possibly via reduction of MDA, TNF-α, IL-6 and IL-17 levels.","PeriodicalId":14582,"journal":{"name":"Iranian Journal of Pharmaceutical Sciences","volume":"14 1","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68025831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deepanjan Dutta, Trishna Bal, Sabyasachi Swain, S. Goswami
{"title":"FABRICATION AND EVALUATION OF PHYSICALLY CROSSLINKED STIMULI SENSITIVE POLYMERIC BLEND OF PVA-GELATIN AS DRUG DELIVERY SYSTEM BY FREEZE THAW CYCLES","authors":"Deepanjan Dutta, Trishna Bal, Sabyasachi Swain, S. Goswami","doi":"10.22034/IJPS.2018.35936","DOIUrl":"https://doi.org/10.22034/IJPS.2018.35936","url":null,"abstract":"Vacuum dried Metronidazole hydrochloride (MTZ) loaded Crosslinked polymeric blend of Poly(vinyl)alcohol (PVA) and Gelatin(GE) in different ratios by 30 freeze/thaw cycles (FTC) tested for stimuli sensitivity and crosslinking at various pH, temperature, ionic concentration and oscillatory test along with dye absorption test showed maximum swelling in alkaline pH and decreased swelling with increased ionic concentration. Digital scanning calorimetry(DSC) thermograms of the blank crosslinked sample showed a sharp endothermic peak at 160.57 0C and MTZ loaded samples showed two sharp endothermic peaks at 159.95 0C and 324.74 0C indicating the entrapment of drug in the polymeric network. Scanning electron microscopy(SEM) showed the rough polymeric texture. Fourier Transformation Infrared Spectroscopy(FTIR) confirmed the presence of new peaks in the cross-linked and drug-loaded sample. In-vitro drug release studies showed 98.253%± 0.363 and 92.248%±0.244 release in the first 6 hours. Biodegradability and bactericidal studies of the blank film indicated that the crosslinked sample is biodegradable and does not inhibit any microbial growth.","PeriodicalId":14582,"journal":{"name":"Iranian Journal of Pharmaceutical Sciences","volume":"14 1","pages":"117-144"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47231697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation the Toxicopathological Lesions of Berberis Vulgaris Using a Chicken Embryonic Model","authors":"A. Derakhshanfar, H. Tavakkoli","doi":"10.22034/IJPS.2018.35930","DOIUrl":"https://doi.org/10.22034/IJPS.2018.35930","url":null,"abstract":"Toxicopathological effects of herbs have always been a major concern. There is scant information available about the toxicopathological effects of barberry in the fetus. Since the embryogenesis in chicken is similar to human beings, the objective of this study is to evaluate the lesions of the various dosages of Berberis vulgaris using a chicken embryonic model. Fertile chicken eggs were divided into four equal treatment groups; phosphate buffered saline-injected group and barberry-injected groups whose individuals were injected with Berberis vulgaris fruit-extract at dosages of 10, 50 and 100 mg per Kg egg-weight, respectively. Embryos were re-incubated post-treatment and allowed to develop until day 18, after which they were examined for macroscopic and microscopic lesions. Results showed that embryos were stunted in the barberry-injected groups. Defect in feather growth and general congestion was accompanied by pathological changes in brain, liver, kidney, heart and lung. Histopathological lesions include congestion, hemorrhage, edema and micro-thrombosis in the affected organs. Based on findings, it is concluded that Berberis vulgaris at the above-mentioned concentrations is toxic to the chicken embryo in a dose dependent manner. Further studies are needed to clarify the toxic effects of this herb on the development of human fetus.","PeriodicalId":14582,"journal":{"name":"Iranian Journal of Pharmaceutical Sciences","volume":"14 1","pages":"79-90"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41763537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigating the Antimicrobial Efficacy of Liposomal Vancomycin in Gram-positive and Gram-negative bacteria- A Preliminary Mechanistic Study","authors":"A. Serri, A. Mahboubi, A. Zarghi, H. Moghimi","doi":"10.22034/IJPS.2018.35924","DOIUrl":"https://doi.org/10.22034/IJPS.2018.35924","url":null,"abstract":"Outer membrane of Gram-negative bacteria is a permeability barrier to many antibacterial agents, including the glycopeptide antibiotics such as vancomycin hydrochloride and as a result these antibiotics are ineffective against Gram negative bacteria. Different strategies have been described to overcome such limitation, including application of nanoparticles, as was shown in our previous studies for polymeric nanoparticles. On the other hand, some nanoparticles have the ability to reduce the permeation of drugs through biological barriers. Therefore, in this investigation, the effects of fusogenic liposomes, which are expected to interact well with biological barriers, toward antimicrobial effects of vancomycin in different bacteria, are investigated. Vancomycin-loaded liposomes were prepared by lipid film hydration method from a phospholipid mixture composed of either DPPC: DOPE: Chol or DPPC: DOPE: CHEMS, both in 1: 0.5: 1 molar ratios. Obtained liposomes were then assessed in regard to their antibacterial properties using broth microdilution method. Liposomes were prepared by lipid-film hydration followed by extrusion and probe sonication for size reduction. Encapsulation efficiency for large hydrophilic vancomycin in liposomes was found to be in the range 0.1 to 9 % for different formulations. Probes sonicated liposomes showed smaller size and were more stable than those prepared by extrusion. Antimicrobial results showed that encapsulation of vancomycin in liposomes decreased antibacterial efficacy of vancomycin and caused MIC increments, compared to those of free vancomycin. This might indicate negligible release of this large and charged molecule from liposomes into the bacterial preplasmic space (retention of vancomycin inside liposomal cavity or lipid-drug complexation) accompanied by inability of liposomes to permeate the bacterial barrier. Further investigations are needed to explain the interaction of liposomes with bacterial membranes.","PeriodicalId":14582,"journal":{"name":"Iranian Journal of Pharmaceutical Sciences","volume":"14 1","pages":"13-24"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47900608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Farimah Rahimi, H. Rasekh, E. Abbasian, F. Peiravian
{"title":"Selecting reference countries in external reference based pricing: The case study of Iran","authors":"Farimah Rahimi, H. Rasekh, E. Abbasian, F. Peiravian","doi":"10.22034/IJPS.2018.35926","DOIUrl":"https://doi.org/10.22034/IJPS.2018.35926","url":null,"abstract":"Most countries are using some kinds of pharmaceutical policies, like external reference-based pricing, to control the costs of medicines. This policy could be implemented in different ways and there is no systematic method for selecting reference countries. In this study, we tried to identify and classify the factors affecting the selection of reference countries in Iran. Delphi method was employed to elicit experts’ opinion in pharmaceutical sector on the parameters affecting the choice of reference countries. Members of the panel were experts in the field of policymaking, manufacturing, distribution and importation of medicines, insurance companies, and academics who were more familiar with the purpose of the research. Panels were run in three rounds. The results of this study reveal that the impact of pharmaceutical, economy and health sectors characteristics has been more effective, in selecting reference countries. Health insurance coverage was the most important index among all the different sectors. Other important indexes included pharmaceutical pricing system, mechanism of drug registration, gross national income (GNI) per capita, health expenditure per capita, health expenditure (share of GDP) and the out-of-pocket health expenditure. To have an efficient pharmaceutical external reference-based pricing, it is important to select reference countries with more similar important parameters. Obviously, any change in these parameters has to be considered and adjusted during the time.","PeriodicalId":14582,"journal":{"name":"Iranian Journal of Pharmaceutical Sciences","volume":"14 1","pages":"36-48"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46328141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}