DARU Journal of Pharmaceutical Sciences195A QSAR study of some cyclobutenediones as CCR1 antagonists by artificial neural networks based on principal component analysis.37684MShahlaeiAFassihiLSaghaieEArkanAPourhossein20151109A quantitative structure activity relationship (QSAR) model based on artificial neural networks (ANN) was developed to study the activities of 29 derivatives of 3-amino-4-(2-(2-(4-benzylpiperazin-1-yl)-2-oxoethoxy) phenylamino) cyclobutenedione as C-C chemokine receptor type 1(CCR1) inhibitors.A feed-forward ANN with error back-propagation learning algorithm was used for model building which was achieved by optimizing initial learning rate, learning momentum, epoch and the number of hidden neurons.Good results were obtained with a Root Mean Square Error (RMSE) and correlation coefficients (R(2)) of 0.189 and 0.906 for the training and 0.103 and 0.932 prediction sets, respectively.The results reflect a nonlinear relationship between the Principal components obtained from calculated molecular descriptors and the inhibitory activities of the investigated molecules.https://daru.tums.ac.ir/index.php/daru/article/view/400

DARU Journal of Pharmaceutical Sciences195Preparation and comparison of chitosan nanoparticles with different degrees of glutathione thiolation.36775PYousefpourFAtyabiRDinarvandEVasheghani-Farahani20151109Chitosan has gained considerable attentions as a biocompatible carrier to improve delivery of active agents. Application of this vehicle in the form of nanoparticle could profit advantages of nanotechnology to increase efficacy of active agents. The purpose of this study was to provide detailed information about chitosan-glutathione (Cht-GSH)nanoparticles which are gaining popularity because of their high mucoadhesive and extended drug release properties.Depolymerization of chitosan was carried out using sodium nitrite method.Glutathione was covalently attached to chitosan and the solubility of the resulting conjugates was evaluated. Nanoparticles were prepared by ionic gelation method and then the effect of glutathione immobilization on properties of nanoparticles was investigated.Thiolation efficiency was higher in lower molecular weight chitosan polymers compared to unmodified chitosan nanoparticles. Cht-GSH conjugates of the same molecular weight but with different degrees of thiolation had the same hydrodynamic diameter (995± nm) and surface charge (102± mV) as unmodified chitosan, but comprised of a denser network structure and lower concentration. Cht-GSH nanoparticles also exhibited greater mucoadhesive strength which was less affected by ionic strength and pH of the environment.Thiolation improves the solubility of chitosan without any significant changes in size and charge of nanoparticles, but affects the nanogel structure.https://daru.tums.ac.ir/index.php/daru/article/view/401

DARU Journal of Pharmaceutical Sciences195Development of diclofenac sodium-loaded alginate-PVP K 30 microbeads using central composite design.35666AkNayakSKhatuaMsHasnainKkSen20151109Diclofenac sodium is a non-steroidal anti-inflammatory agent with a short biological half-life (1-2 hr) and requires multiple dosing. This research was carried out to develop and optimize diclofenac sodium loaded alginate-PVP K 30 microbeads to eliminate the need for multiple dosing and adverse effects.Diclofenac sodium loaded alginate-PVP K 30 microbeads were prepared by ionotropic gelation. Particle size, drug release, swelling, FTIR and SEM analyses were performed.Optimized microbeads showed particle size of 0.589±0.054 to 0.620±0.067 mm, and drug entrapment efficiency of 97.88±2.86 to 98.60±3.55%. The in vitro drug release from microbeads was sustained over 10 hrs and followed controlled-release pattern. FTIR analysis indicated the possibility of intermolecular hydrogen bonding interactions, i.e., -OH…O=C in microbeads.Microbeads for oral controlled delivery of diclofenac sodium were successfully developed by ionotropic gelation.https://daru.tums.ac.ir/index.php/daru/article/view/402

DARU Journal of Pharmaceutical Sciences195Preparation and antifungal activity of spray-dried amphotericin B-loaded nanospheres.3515AGharibZFaezizadehHMohammad Asghari20151109Amphotericin B (AmB) which is an appropriate antibiotic for the treatment of mycosis has many toxic effects including nephrotoxicity. Recently preparation of a new drug loaded nanoparticles for the reduction of toxicity and increase in the effectiveness of AmB has been reported. The objective of this study was to prepare and evaluate in vitro and in vivo efficacy of the spray-dried AmB-loaded nanospheres.AmB-loaded nanospheres was prepared by means of nanoprecipitation method. The spray-dried nanospheres was prepared by using aerosil and AmB entrapment efficacy was measured by HPLC method. Minimum inhibitory concentration (MIC) of AmB-loaded nanospheres against Candida albicans (ATCC 90028) was determined by using microdilution method and its in vitro haemolytic effect and antifungal efficacy on infected rabbits was also analyzed.The entrapment efficacy for AmB loaded nanospheres was 65.2%±3. The MIC of AmB-loaded nanospheres against C. albicans compared to the free antibiotic was lower significantly. Also, the AmB-loaded nanospheres found to be 9.5 times less toxic than free AmB on human red blood cells. In vivo testing indicated that AmB-loaded nanospheres have a stronger protective effect against candidiasis compared to the free AmB.Results of this study suggest that prepared spray-dried AmB-loaded nanospheres would be a good choice for the treatment of mycosis because of low toxicity and high stability and effectiveness.https://daru.tums.ac.ir/index.php/daru/article/view/403

DARU Journal of Pharmaceutical Sciences195Formulation and in vivo evaluation for anti-aging effects of an emulsion containing basil extract using non- invasive biophysical techniques.34450ARasulNAkhtar20151109BACKGROUND AND THE PURPOSE OF STUDY: Skin aging is a complex process induced by constant exposure to ultraviolet (UV) irradiation and damages human skin. UV generates reactive oxygen species leading to collagen deficiency and eventually skin wrinkling. Basil contains a number of phenolics and favonoids which possess antioxidant properties. The aim of this study was to formulate and investigate the antiaging potential of a cream containing Basil extract.A single blinded study was conducted using non-invasive methods. Formulation containing 3% of the concentrated extract of Basil was developed by entrapping in the inner aqueous phase of w/o emulsion and base contained no extract. Both creams were stored at different storage conditions of 8°C, 25°C, 40°C and 40°C+ 75% relative humidity to predict their stabilities. The formulation and base were evaluated for their effects on various skin parameters i.e., moisture and trans epidermal water loss (TEWL), volume, energy and surface evaluation of the living skin (SELS).Significant effects (p≤0.05) were observed for both creams in the case of TEWL. The base showed insignificant (p≤0.05) while formulation showed significant effects on skin moisture. Volume, SELS SEr (skin roughness), SEsc (skin scaliness), SEsm (skin smoothness), SEw (skin wrinkles) parameter showed significant decline while texture parameter of 'Energy' showed significant increase.The results statistically indicated that the active formulation containg extract of Basil exert antiaging effects when applied topically.https://daru.tums.ac.ir/index.php/daru/article/view/404

DARU Journal of Pharmaceutical Sciences1955-HT(1A) receptor activation improves anti-cataleptic effects of levodopa in 6-hydroxydopamine-lesioned rats.33843JMahmoudiAMohajjel NayebiMSaminiSReyhani-RadVBabapour20151109In Parkinson›s disease (PD) prolong use of L-DOPA causes some motor disorders such as wearing-off and L-DOPA induced dyskinesia (LID). In this investigation the effect of 8-OHDAPT, as a 5-HT(1A) agonist on anti-cataleptic effect of L-DOPA in 6-hydroxydopamine (6-OHDA) lesioned male Wistar rats was investigated.Catalepsy was induced by unilateral injection of 6-OHDA (8 µg/2µl/rat) into the central region of the SNc. After 3 weeks as a recovery period, animals received intraperitoneally (i.p.) L-DOPA (15 mg/kg) twice daily for 20 days, and anti-cataleptic effect of L-DOPA was assessed by bar-test at days of 5, 10, 15 and 20.The results showed that L-DOPA had anti-cataleptic effect only until the day of 15, and its effect was decreased on the day of 20. On the day of 21, rats were co-injected with three different doses of 8-OHDAPT (0.1, 0.5 and 2.5 mg/kg, i.p.) and L-DOPA (15 mg/kg, ip). 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OHDAPT) improved anti-cataleptic effect of L-DOPA at the dose of 0.5 mg/kg. Moreover the effect of 8-OHDAPT on anti-cataleptic effect of L-DOPA (15 mg/kg, ip) was abolished by 1-(2-methyoxyphenyl)-4-[4-(2-phthalamido) butyl] piperazine hydrobromide (NAN-190; 0.5 mg/kg, i.p.) as a 5-HT(1A) receptor antagonist. According to the obtained results, it may be concluded that activation of 5-HT(1A) receptors by 8-OHDAPT may improve anti-cataleptic effect of L-DOPA in a 6-OHDA- induced rat model of PD. Further studies are required to clarify the exact mechanism of interaction between 5-HT(1A) and dopaminergic neurons.https://daru.tums.ac.ir/index.php/daru/article/view/405

DARU Journal of Pharmaceutical Sciences195The presence of amorpha-4, 11-diene synthase, a key enzyme in artemisinin production in ten Artemisia species.3327RHosseiniNYazdaniGaGaroosi20151109Artemisinin is one of the most effective medicine against malaria, which is produced naturally by Artemisia annua in low yield. It is produced in a metabolic pathway, in which several genes and gene products are involved. One of the key genes in this pathway is am1, which encodes amorpha-4, 11-diene synthase (ADS), a key enzyme in artemisinin biosynthesis pathway. The aim of this study was to determine the presence of this gene in ten Artemisia species in order to increase the yield of production of Artemisinin.The experiments were carried out using PCR. Specific primers were designed based on the published am1 gene sequence obtained from A. annua (NCBI, accession number AF327527).The amplification of this gene by the specific primers was considered as a positive sign for the potentiality of artemisinin production. Since the entire am1 gene was not amplified in any of the 10 species used, four parts of the gene, essential in ADS enzyme function, corresponding to a) pair site of Arg10-Pro12 in the first 100 amino acids, b) aspartate rich motif (DDXXD), c) active site final lid and d) active site including farnesyl diphosphate (FDP) ionization sites and catalytic site in the ADS enzyme, were investigated.The sequence corresponding to ADS active site was amplified only in A. annua, A. aucheri and A. chamaemelifolia. The negative results obtained with other species could be due to some sequence alteration, such as point mutations or INDELs. We propose A. aucheri and A. chamaemelifolia as two potential candidate species for further characterization, breeding and transferring am1 gene for artemisinin overproduction.https://daru.tums.ac.ir/index.php/daru/article/view/406

DARU Journal of Pharmaceutical Sciences195Effects of polygonum aviculare herbal extract on proliferation and apoptotic gene expression of MCF-7.32631Roudkenar MHabibiRoushandeh AMohammadiADelazarRHalabianRad JSoleimaniAMehdipourMBagheriAJahanian-Najafabadi20151109One of the most common malignancies in women is breast cancer. Although several treatments for breast cancer are available, application of herbal medicine as a supplementary treatment is a new option to help curing the disease. In this study anticancer effects of Polygonum avicular herbal extract was investigated.Polygonum avicular extract was obtained by methanol. MCF-7 cell line was treated with different concentrations of Polygonum avicular (50, 100, 150, 200, 250, 300,350 400 ng/µl) for different time lengths ( 6, 12, 24, and 48 hrs). MTT assay and Flow Cytometry were used to evaluate cell proliferation and apoptosis, respectively. RT-PCR was also carried out to evaluate the expression of apoptotic genes.Results showed that Polygonum avicular induced cytotoxicity in MCF-7 cell line at concentrations higher than 300 ng/µl and this was confirmed by the highest rate of cell death as measured by Trypan Blue and MTT assays. RT-PCR results showed up-regulation of P53 and down-regulation of Bcl-2 proteins which implied the ability of Polygonum avicular to induce apoptosis in MCF-7 cells and confirmed its anticancer property. Further studies are required to evaluate effects of the extract on other apoptotic genes.https://daru.tums.ac.ir/index.php/daru/article/view/407

DARU Journal of Pharmaceutical Sciences195Renoprotective effects of combining ACE inhibitors and statins in experimental diabetic rats.3225MMudagalJPatelNcNagalakshmiMAsif Ansari20151109The combination of angiotensin II receptor antagonists and HMG CoA reductase inhibitors have shown to confer renoprotection.The purpose of this study was to find out the renoprotective effects of telmisartan and atorvastatin in combination and in monotherapy of Streptozotocin (STZ) induced diabetic nephropathy in rats.Diabetes was induced by i.p injection of STZ to rats, after 18 hrs of fasting. Diabetic rats were randomly grouped and treated with telmisartan and atorvastatin in combination as well as monotherapy for 30 days. The serum and urine glucose, creatinine and serum triglyceride, cholesterol, albumin and micro-albumin and blood urea nitrogen, total protein and histological analyses of the left kidney were performed at the end of the study.By the end of the study, the combination showed significant (P < 0.05) improvement in urine glucose, serum cholesterol, serum and urine creatinine, blood urea nitrogen, total protein, serum albumin, micro-albuminuria levels in comparison to monotherapy. However, this combination didn't show significant changes on serum glucose and triglyceride levels. Kidney pathological injury was attenuated by the combination as compared to the diabetic group.The present study document that, telmisartan and atorvastatin combination have better renoprotective effects but not with individual drug when compared to the diabetic group. The combination also attenuated the progression of diabetic nephropathy by slowing the proteinuria and microalbuminuria and these effects were confirmed by histopathological analysis.https://daru.tums.ac.ir/index.php/daru/article/view/408

DARU Journal of Pharmaceutical Sciences195A systematic review on pharmacokinetic changes in critically ill patients: role of extracorporeal membrane oxygenation.31221SMousaviBLevcovichMMojtahedzadeh20151109Several factors including disease condition and different procedures could alter pharmacokinetic profile of drugs in critically ill patients. For optimizing patient's outcome, changing in dosing regimen is necessary. Extracorporeal Membrane Oxygenation (ECMO) is one of the procedures which could change pharmacokinetic parameters.The aim of this review was to evaluate the effect of ECMO support on pharmacokinetic parameters and subsequently pharmacotherapy.A systematic review was conducted by reviewing all papers found by searching following key words; extracorporeal membrane oxygenation, ECMO, pharmacokinetic and pharmacotherapy in bibliography database.Different drug classes have been studied; mostly antibiotics. Almost all of the studies have been performed in neonates (as a case series). ECMO support is associated with altered pharmacokinetic parameters that may result in acute changes in plasma concentrations with potentially unpredictable pharmacological effect. Altreation in volume of distribution, protein binding, renal or hepatic clearance and sequestration of drugs by ECMO circuit may result in higher or lower doses requirement during ECMO. As yet, definite dosing guideline is not available. ECMO is extensively used recently for therapy and as a procedure affects pharmacokinetics profile along with other factors in critically ill patients. For optimizing the pharmacodynamic response and outcome of patients, drug regimen should be individualized through therapeutic drug monitoring whenever possible.https://daru.tums.ac.ir/index.php/daru/article/view/409