Research in Pharmaceutical Sciences
Volume:9 Issue: 6, Dec 2014

Silver nanoparticles (NPs) have been the subjects of researchers because of their unique properties (e.g., size and shape depending optical, antimicrobial, and electrical properties). A variety of preparation techniques have been reported for the synthesis of silver NPs; notable examples include, laser ablation, gamma irradiation, electron irradiation, chemical reduction, photochemical methods, microwave processing, and biological synthetic methods. This review presents an overview of silver nanoparticle preparation by physical, chemical, and biological synthesis. The aim of this review article is, therefore, to reflect on the current state and future prospects, especially the potentials and limitations of the above mentioned techniques for industries.

Double emulsion solvent evaporation technique is one of the most attractive methods used to prepare micro and nanoparticles in pharmaceutical areas of interest, but because of the effects of many formulation factors on the size and release behavior of the fabricated particles, optimization of the formulation factors is needed. In this study various parameters including technical and compositional variables were considered to achieve an optimized formulation with desire characteristics especially size and the release profiles, using high shear homogenizer. In this regard, bovine serum albumin (BSA) was used as the model protein and double emulsion was formed with the addition of Tween 80 and Span 80 as surfactants for inner aqueous phase and oil phase, respectively. Hydroxypropyl beta cyclodextrin was used as protein stabilizer. After optimization steps, composite nanoparticles (core-shell) were made based on optimized formulation by hyaluronic acid as shell and poly lactic-co-glycolic acid (PLGA) as core material. Formulation of the BSA loaded PLGA nanoparticles using core shell strategy improved the release pattern of the BSA and diminished burst release. The final composite nanoparticles had the particle size of about 160 nm and 70 % of the loaded BSA was released during 14 days and the release data was better fitted to zero order release kinetics.

Prunus divaricata (Alloocheh) is a small tree cultivating in Iran, Middle East and central Asia. Prunus genus has many species with anti-oxidant, anti-hyperlipidemia and anti-hyperglycemia effects. In the present study the anti-diabetic and anti-hyperlipidemic effects of P. divaricata fruits were examined in normal and streptozotocin (STZ)-induced diabetic rats. Both groups, control and reference rats received normal saline and glibenclamide respectively. Test groups were treated with Prunus freeze dried juice (PFDJ, 200, 400, 800 mg/kg) and Prunus freeze dried extract (PFDE, 100, 200, 400 mg/kg) started at the 3rd day of the experiment and continued for 27 days thereafter. Weight changes of animals were checked periodically. Fasting blood glucose (FBG) level as well as serum triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol were determined. Different treatments had no significant effect on body weight increments of normal rats, while in diabetic rats, PFDJ (800 mg/kg) and PFDE (400 mg/kg) opposed with weight loss. In acute phase of experiment (0-8 h of 3rd day), none of tested fractions were effective in reducing FBG and serum lipids of normal rats. During the sub-acute phase (13th and 30th days) however, the greatest test doses of PFDJ (800 mg/kg) and PFDE (400 mg/kg) induced hypoglycema. In diabetic groups, PFDJ and PFDE, at all test doses, could diminish FBG during sub-acute phase of the experiment. In addition, PFDJ and PFDE at most examined doses could diminish TG significantly and they were also effective on cholesterol derivatives in different magnitude.

Amyloid pathology is associated with fibril aggregation of different proteins which results in the progressive damage of affected organs. It is strongly believed that specific small molecules interfere with fibrillation by interacting with the amyloidogenic proteins. We had previously reported the strong and long-term inhibition of fibrillation of hen egg white lysozyme (HEWL) by Cuminum cyminum oil. Herein, it was intended to rationally identify the active anti-amyloidogenic compounds of the oil. After fractionation, the highest inhibitory effect was observed in the toluene-ethyl acetate part of the oil. Gas chromatography-mass spectrometry (GC-MS) analysis of this fraction indicated that eight compounds were predominantly present in the fraction. Unexpectedly, two compounds including terpinolene and limonene, having very similar chemical structures, inhibited and induced fibrillation, respectively. PC12 cells (derived from a transplantable rat pheochromocytoma) were affected by HEWL fibrils, whereas the inhibited forms of fibrils in the presence of terpinolene led to higher levels of viability, as shown by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) and flow cytometry assays. Molecular local docking analysis suggested a site of interaction for terpinolene in the flexible cleft of the protein. This interaction site is close to tryptophan -62 and -63 and two other hydrophobic residues in the hot spot regions of the protein. Seemingly, these interactions interrupt protein self-assembly and therefore, fibril formation. Despite previously reported small anti-amyloid molecules which have aromatic flat rings, terpinolene ring is not flat. This functionally durable small molecule may aid us toward developing new anti-amyloidogenic compounds with extended activity.

We have previously evaluated the effect of nimodipine, L-type calcium channel blocker, on memory loss during spontaneous morphine withdrawal. In the present study the effect of nimodipine on memory loss in naloxone-induced morphine withdrawal mice was investigated. Mice were made dependent by increasing doses of morphine for three days. Object recognition task that was used for evaluation of memory performance comprised of three sections: 15 min habitation, 12 min first trial and 5 min test trial. Naloxone was injected 3 h after the administration of the last dose of morphine. Recognition index was evaluated 20 min after naloxone injection. Nimodipine was administrated in repeated form (1, 5 and 10 mg/kg) with daily doses of morphine or as a single injection (5 and 10 mg/kg) on the last day. Both acute and repeated treatments with nimodipine prevented the memory impairment in naloxone-induced morphine withdrawal mice (P<0.05 comparison of acute and repeated treatment data with their corresponding control values). Corticosterone concentration was significantly increased in the brain and blood of the mice during withdrawal. Pretreatment with nimodipine, however, decreased the corticosterone concentration in both brain and blood. The present study showed that nimodipine prevents intense memory loss following naloxone-induced morphine withdrawal.

Human Insulin-like growth factor 1 (hIGF-1) consists of 70 amino acids in a single chain with three intermolecular disulfide bridges possessing valuable therapeutic effects. To date, numerous variants of specifically engineered hIGF-1 have been produced so as to improve hIGF-1 biological activity, stability and stronger binding to IGF-1 receptor. Mecasermin is one of the modified variants with one amino acid substitution near the N-terminal (T4I) approved for the treatment of growth failure diabetes, wound healing, amyotrophic lateral sclerosis and severe primary IGF-1 deficiency. No scientific report for recombinant production of mecasermin in Escherichia coli (E. coli) expression system has been sofar reported. In the present study, we therefore investigated the overexpression of mecasermin in two different E. coli strains in order to obtain higher yield of recombinant protein. To achieve this goal, mecasermin DNA encoding sequence was designed based on polypeptide sequence, optimized according to E. coli codon preference, and cloned in pET15b. Recombinant vector, pET15-mecasermin, transferred into two E. coli strains rigami B (DE3) and BL21 (DE3) and induced for expression in a small scale. Results revealed the E. coli Origami B (DE3) expression system was a preferable host for mecasermin production due to its high expression level being around twice as much as BL21 (DE3). Large scale mecasermin production was performed in batch culture and produced recombinant protein specifically confirmed by western blotting and mass spectroscopy. Since major part of recombinant mecasermin was expressed as inclusion body, isolation and refolding was accomplished through developed purification procedure, and finally recombinant protein was successfully purified by gel filtration chromatography.

Previously, we reported that the kaempferol and kaempferol-7-O-glucoside isolated from Securigera securidaca showed potent anti-HSV activity. In the present study the anti-HIV-1 activities of kaempferol and kaempferol-7-O-glucoside are investigated at different concentrations (100, 50, 25 and 10 µg/ml) using HIV-1 p24 Antigen kit. Real-time Polymerase chain reaction (RT-PCR) assay was also used for quantification of full range of virus load observed in treated and untreated cells. According to the results of RT- PCR, tested compounds at a concentration of 100 µg/ml exerted potent inhibitory effect. Time of drug addition experiments demonstrated that these compounds exerted their inhibitory effects on the early stage of HIV infection. The results also showed potent anti-HIV-1 reverse transcriptase activity. Antiviral activity of kaempferol-7-O-glucoside was more pronounced than that of kaempferol. These findings demonstrate that kaempferol-7-O-glucoside could be considered as a new potential drug candidate for the treatment of HIV infection which requires further assessments.

A quantitative structure–activity relationship (QSAR) study is suggested for the prediction of biological activity (pIC50) of 3, 4-dihydropyrido [3, 2-d] pyrimidone derivatives as p38 inhibitors. Modeling of the biological activities of compounds of interest as a function of molecular structures was established by means of principal component analysis (PCA) and least square support vector machine (LS-SVM) methods. The results showed that the pIC50 values calculated by LS-SVM are in good agreement with the experimental data, and the performance of the LS-SVM regression model is superior to the PCA-based model. The developed LS-SVM model was applied for the prediction of the biological activities of pyrimidone derivatives, which were not in the modeling procedure. The resulted model showed high prediction ability with root mean square error of prediction of 0.460 for LS-SVM. The study provided a novel and effective approach for predicting biological activities of 3, 4-dihydropyrido [3,2-d] pyrimidone derivatives as p38 inhibitors and disclosed that LS-SVM can be used as a powerful chemometrics tool for QSAR studies.

The functional role of the exon 3 growth hormone receptor (d3GHR) polymorphism in human and its distributions in different populations is not clearly understood. The presence of full length growth hormone (flGHR) is the most important in metabolic risk factors. The aim of this study was to define the frequency distribution of d3GHR/full-length GHR in an Iranian population. The presence of the d3GHR polymorphism in healthy volunteers blood DNA (n=80, male=30 and female=50) was assessed by PCR using specific primers. The 935-bp and 592-bp fragments indicate the presence of the flGHR and the exon3 deletion of GHR, respectively. The distribution of the GHR genotypes in this study were 31.4% (n=24) for fl/flGHR, 49.7 % (n=41) for fl/d3GHR, and 19.0 % (n=15) for d3/d3GHR. Frequencies of fl allele and d3 allele were 55.4% and 44.4% within whole population, respectively. There was no difference in allels frequencies of GHR in male (fl=0.583, d3=0.417) and female (fl=0.540, d3=0.460) when compared with whole population. The results showed that the frequency of d3/d3GHR isoform was significantly lower than that of the fl/flGHR and d3/flGHR. The frequencies of GHR polymorphisms were likely consistent with previous reports. Our finding is also consistant with Mexican population. The advantage of existence of the d3/d3 rather than fl/flGHR polymorphisms in individuals and in correlation with diseases opens new insights for GH and insilin-like-growth factor-1 (IGF-I) axis.