Iranian Journal of Pharmaceutical Research最新文献

Background: As an environmental contaminant, Arsenic (As) poses many risks to human health. Increased Oxidative Stress (OS) and decreased antioxidant cell defense are the suggested mechanisms of carcinogenicity and toxicity of As. As a powerful antioxidant and water-soluble compound, vitamin C protects cells and tissues against oxidation and has a wide range of healing properties.

Objectives: The current study aimed to formulate a suitable ascorbic acid (vitamin C) niosome and compare it with vitamin C in preventing As-induced toxicity in HEK-293 cells.

Methods: Various formulas of vitamin C niosomes were prepared by C-SPAN mixed with cholesterol. The physicochemical characteristics of niosomal formulations, including load size, zeta-potential, and the drug release profile, were evaluated in HEK-293 cells. Then, OS biomarkers such as total reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), Antioxidant Capacity (TAC), and superoxide dismutase (SOD) activities determined the protective effects of vitamin C niosomes compared with vitamin C against As-induced toxicity.

Results: The particle size and zeta potential of the optimal vitamin C niosome were 163.2 ± 6.1 nm and 23.3 ± 3.5 mV, respectively. Arsenic increased ROS and MDA levels while decreasing CAT, TAC, and SOD activities in the HEK-293 cell line. Finally, the vitamin C niosome decreased OS and increased antioxidant properties more than vitamin C.

Significance: Vitamin C niosome was more effective than vitamin C in treating As-induced toxicity in vitro.

Context: The whole universe is facing a coronavirus catastrophe, and prompt treatment for the health crisis is primarily significant. The primary way to improve health conditions in this battle is to boost our immunity and alter our diet patterns. A common bulb veggie used to flavor cuisine is garlic. Compounds in the plant that are physiologically active are present, contributing to its pharmacological characteristics. Among several food items with nutritional value and immunity improvement, garlic stood predominant and more resourceful natural antibiotic with a broad spectrum of antiviral potency against diverse viruses. However, earlier reports have depicted its efficacy in the treatment of a variety of viral illnesses. Nonetheless, there is no information on its antiviral activities and underlying molecular mechanisms.

Objectives: The bioactive compounds in garlic include organosulfur (allicin and alliin) and flavonoid (quercetin) compounds. These compounds have shown immunomodulatory effects and inhibited attachment of coronavirus to the angiotensin-converting enzyme 2 (ACE2) receptor and the Mpro of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Further, we have discussed the contradictory impacts of garlic used as a preventive measure against the novel coronavirus.

Method: The GC/MS analysis revealed 18 active chemicals, including 17 organosulfur compounds in garlic. Using the molecular docking technique, we report for the first time the inhibitory effect of the under-consideration compounds on the host receptor ACE2 protein in the human body, providing a crucial foundation for understanding individual compound coronavirus resistance on the main protease protein of SARS-CoV-2. Allyl disulfide and allyl trisulfide, which make up the majority of the compounds in garlic, exhibit the most potent activity.

Results: Conventional medicine has proven its efficiency from ancient times. Currently, our article's prime spotlight was on the activity of Allium sativum on the relegation of viral load and further highlighted artificial intelligence technology to study the attachment of the allicin compound to the SARS-CoV-2 receptor to reveal its efficacy.

Conclusions: The COVID-19 pandemic has triggered interest among researchers to conduct future research on molecular docking with clinical trials before releasing salutary remedies against the deadly malady.

Background: Stimuli-responsive drug delivery systems have been proven to be a promising strategy to enhance tumor localization, overcome multidrug resistance (MDR), and reduce the side effects of chemotherapy agents.

Objectives: In this study, a temperature and redox dual stimuli-responsive system using mesoporous silica nanoparticles (MSNs) for targeted delivery of doxorubicin (DOX) was developed.

Methods: Mesoporous silica nanoparticles were capped with poly(N-isopropylacrylamide) (PNIPAM), a thermo-sensitive polymer, with atom transfer radical polymerization (ATRP) method, via disulfide bonds (DOX-MSN-S-S-PNIPAM) to attain a controlled system that releases DOX under glutathione-rich (GSH-rich) environments and temperatures above PNIPAM's lower critical solution temperature (LCST). Morphological and physicochemical properties of the nanoparticles were indicated using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Brunauer-Emmett-Teller (BET). The drug release tests were performed at 25°C and 41°C in the absence and presence of the DTT, and the obtained results confirmed the synergic effect of temperature and reductive agent on a dual responsive release profile with a 73% cumulative release at 41°C and reductive environment during 240 min.

Results: The average loaded drug content and encapsulation efficacy were reported as 42% and 29.5% at the drug: nanoparticle ratio of 1.5: 1. In vitro cytotoxicity assays on MCF-7 cell lines indicated significant viability decreased in cells exposed to DOX-MSN-S-S-PNIPAM compared to the free drug (DOX).

Conclusions: Based on the results, DOX-MSN-S-S-PNIPAM has shown much more efficiency with stimuli-responsive properties in comparison to DOX on MCF-7 cancer cell lines.

The human body produces two classes of antimicrobial peptides (AMPs), namely defensins and cathelicidins. In this study, a novel decapeptide (Catoid) and its dimer (Dicatoid) based on human cathelicidin (LL-37) have been designed by bioinformatics tools to be used in the treatment of bacterial keratitis. After the selection and synthesis of peptide sequences, their antimicrobial activities against the standard and resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus were evaluated. This test was performed with LL-37, gentamicin, ciprofloxacin, amikacin, and penicillin for a more accurate comparison. Furthermore, the cytotoxicity levels of the specified compounds on fibroblast cells and bovine corneal endothelial cells were investigated. The results demonstrated that the designed peptides had a superior antimicrobial activity on P. aeruginosa, compared to LL-37; however, Catoid had a better effect on the S. aureus strain. Additionally, a significant achievement is the very low toxicity level of Catoid and Dicatoid on the human skin fibroblast cell line and bovine corneal endothelial cells, compared to that of LL-37 as the initial design model.

Background: Despite the favorable progress in the production of medicines, there is no significant access to these important health inputs among different socio-economic groups.

Objectives: This study aimed to measure and explain socio-economic inequality in prescribed and non-prescribed medicine use in Iran.

Methods: Data were obtained from a recent household survey on health services in Iran conducted in 2016. The Erreygers concentration index (ECI) was used to measure socio-economic inequality in the use of prescribed and non-prescribed medicines. In addition, Decomposition analysis was conducted to explain socio-economic inequality.

Results: The ECI revealed pro-rich socio-economic inequality in prescribed medicine use (ECI = 0.067, SE = 0.010), indicating that prescribed medicine use was concentrated on the better-offs. On the other hand, this index showed pro-poor inequality in non-prescribed medicine use (ECI = -0.064, SE = 0.009). Decomposition analysis showed that economic status and place of residence were the main determinants of socio-economic inequality in prescribing medicines. These factors and the number of health care needs explained the majority of socio-economic inequality in non-prescribed medicine use.

Conclusions: Despite previous positive beliefs, we found remarkable socio-economic inequality in the use of medicines in Iran. Facilitating access to pharmaceutical services for disadvantaged households and rural residents and promoting of national essential medicines list could be recommended against socio-economic inequality in the pharmaceutical market of Iran.

Background: Recently, a few studies based on anti-factor Xa activity levels have propounded doubtful and sub-prophylactic levels by the usual dose of enoxaparin in surgical and critically ill patients. In this study, we assessed two doses of enoxaparin in adult non-critically ill patients.

Methods: Patients were randomly assigned into two groups of intervention and control. While the intervention group received enoxaparin with a daily dose of 60 mg, the control group received enoxaparin 40 mg. Anti-factor Xa activity was measured based on the peak steady-state levels. The level of 0.2 to 0.4 IU/mL was considered as a prophylactic goal. All individuals were followed for bleeding or thromboembolic events during admission.

Results: The mean levels of anti-factor Xa were 0.29 ± 0.13 IU/mL in the control group (n = 31) and 0.44 ± 0.19 IU/mL in the intervention group (n = 29). More patients in the control group had an optimal level of anti-factor Xa compared to the patients in the intervention group (62.1% vs. 29%). No adverse outcomes were detected in any of the groups.

Conclusions: Enoxaparin dose of 60 mg daily provided anti-factor Xa level higher than desired in most patients. In non-critically ill patients, the dose of 40 mg is the proper dose for thromboprophylaxis.

Background: Overexpression of CD20 protein on the surface of B cells in lymphoma can be targeted by several anti-CD20 molecules. The development of accessible interactive epitopes is more favorable than the full-length transmembrane CD20 in the affinity assessment of anti-CD20 monoclonal antibodies (mAbs).

Methods: The sequence of these epitopes was extracted, and the effects of different linker peptides and the location of histidine (His)-tag were computationally analyzed. The impact of thioredoxin (Trx)-tag on the folding of the selected construct and its interaction with rituximab was further investigated. The two final expression cassettes were expressed in Escherichia coli after optimization of culture conditions for incubation temperature, post-induction time, optical density at the induction time, and concentration of the inducer. ELISA evaluated the binding affinity of rituximab towards the recombinant proteins.

Results: By homology modeling studies, C-terminal His-tagged structures represented more desirable folded structures. Validation of the models revealed that CD20 extracellular domain linked by the G₄S polypeptide had better stereochemical quality and structural compatibility. It was selected due to its more effective interaction with rituximab showing the highest dissociation constant of 5.8E-09M, which improved after the fusion of Trx-tag (7.1E-10M). The most influential parameters in the expression of the two selected proteins were post-induction temperature and optical density at the induction time. Homemade ELISA assays revealed a slightly higher affinity of rituximab towards the Trx-CD20 protein than the CD20/G₄S molecule.

Conclusions: Experimental in vitro studies confirmed the computationally calculated affinity of rituximab towards the two designed CD20 constructs. Also, the cell-based binding assessment of anti-CD20 mAbs could be substituted by the engineered extracellular domain of human CD20 protein.

Plasma therapy and the study of the effects of cold atmospheric plasma (CAP) on tissues and living cells have been considered by scientific researchers in recent years. CAP is used in the treatment of cancer, but its anti-cancer mechanism has not been fully studied. Therefore, we studied the toxicity effect of CAP by using argon as feed gas and the synergistic effects of CAP with cisplatin on tumor cells and mitochondria isolated from tumor legions of the rat model of oral squamous cell carcinoma (OSCC). For this reason, we determined the possible toxic alterations of CAP on mitochondrial upstream events and activation of caspase-3 as the key major downstream event of apoptosis. Also, the effects of cisplatin (10 µM) as a positive control and its synergistic effects with CAP (IC₅₀ concentration) were investigated. The results showed that CAP reduced mitochondrial dysfunction by reduction in succinate dehydrogenase (SDH) activity. Also, CAP in concentrations of 1200, 2400, and 4800 a.u. has been able to increase the level of reactive oxygen species (ROS), mitochondrial swelling, damage to the mitochondrial membrane, cytochrome c release, and activation of the final mediator of apoptosis (caspase-3) only in the OSCC group. CAP at 4800 a.u concentration had similar effects to cisplatin (10 µM). Synergistic effects between CAP (2400 a.u) and cisplatin (10 µM) have also been reported. Based on all results CAP showed positive and promising results on mitochondrial upstream parameters leading to activation of caspase-3, the final mediator of apoptosis only on OSCC cells and mitochondria without any significant effect on normal cells and mitochondria.

In recent decades, a growing interest has been observed among pharmaceutical companies in producing and selling 80 FDA-approved therapeutic peptides. However, there are many drawbacks to peptide synthesis at the academic and industrial scales, involving the use of large amounts of highly hazardous coupling reagents and solvents. This review focuses on hideous and observant wastes produced before, during, and after peptide synthesis and proposes some solutions to reduce them.

Tau, as a small protein in neurons, plays a main role in stabilizing and assembling the internal microtubules. Here, the effects of antiepileptic drugs, including lamotrigine (LTG) and phenobarbital (PHB), on tau protein structure have been investigated by surface plasmon resonance (SPR), fluorescence spectroscopy along molecular modeling. Fluorescence data analysis revealed that both drugs quench the intrinsic emission intensity of tau protein via a static quenching mechanism. Analysis of SPR data at three different temperatures revealed that binding of LTG and PHB to tau protein leads to a decrease and increase in equilibrium constants (K_D) values with increasing temperature, respectively. Therefore, the affinity of LTG decreases and PHB increases with increasing temperature. In addition, molecular docking studies indicated that both LTG and PHB bind to the S1 pocket of tau protein. Our data demonstrated the preventive effect of two important antiepileptic pharmaceuticals on the aggregation of tau protein. Given that any damage to the tau protein possibly leads to neurodegenerative diseases, this study can provide useful and important information and a basis for further research and study to treat tauopathy.