Iranian Journal of Pharmaceutical Research最新文献

Background: A large number of new substances have insufficient biopharmaceutical properties for oral administration caused by their slow dissolution rate and poor solubility.

Objective: The purpose of our experiment was to improve the physicochemical properties of a hydrophobic drug, quercetin, by the nanomilling approach.

Methods: Quercetin nanosuspensions were prepared using a wet-milling method followed by lyophilization. Stabilizer type and ratio, drug content, milling time, and bead size were identified as critical variables, and their impacts on quercetin particle size were assessed. The optimized nanocrystal was characterized by its morphology, crystallinity, molecular interactions, saturation solubility, and dissolution properties.

Results: At optimized process conditions of milling at 500 rpm for 18 cycles of grinding with 0.3 - 0.4 mm zirconium oxide beads, minimum particle size, and PDI values were 281.21 nm and 0.22, respectively. Nanocrystals showed rod-like nanostructures, and XRD scans confirmed a decrease in drug crystallinity. The optimized formulation showed increased solubility and dissolution rate, as well as good physical stability.

Conclusions: Particle size reduction by media milling technique was an efficient method for the solubility enhancement of hydrophobic drugs.

Background: The supply chain of pharmaceuticals and medical devices takes on critical importance regarding group purchasing, given its contribution to a country's healthcare system. One of the primary loops in this chain is the pharmacy as a supplier of goods to consumers and a buyer of goods from distributors.

Objectives: Given the importance of proper and productive preparation, this study examined the structure of aggregated procurement of drugs and medical supplies in public pharmacies.

Methods: This study used a qualitative method and interviews to collect the necessary data. Fourteen experts and specialists in the public pharmacy field were interviewed and selected using the purposive sampling method. Finally, the textual data were analyzed using efficient thematic analysis.

Results: According to experts, the organizational structure for aggregated procurement of medicines and medical supplies in Iran's public pharmacies can take the form of a headquarters structure, a virtual structure, and a semi-centralized virtual structure. The main requirements for these structures are software infrastructure, a productive workforce, and improved storage methods.

Conclusions: According to the majority of experts, the most desirable structure for implementing aggregated procurement in hospital pharmacies is the headquarters structure. The aggregated procurement process can reduce pharmacy costs and increase financial reserves and profitability if adequately implemented and equipped with the necessary infrastructure.

The COVID-19 pandemic has prompted researchers to find treatments and vaccines to control SARS-CoV-2. There are some hypotheses about the benefit of respiratory virus vaccines, like MMR, for COVID-19 pneumonia severity, morbidity, and mortality. The influenza vaccine is one of the most frequently used respiratory virus vaccines covered by one of the Iranian insurance institutes. We have a symmetrical group of participants that have received this vaccine that could be compared with each other. We compared 3,379 persons aged 20 - 75 years for the effect of the influenza vaccine on COVID-19 mortality. We ultimately found that it does not affect mortality caused by COVID-19 pneumonia, but it can decrease the hospitalization cost in people over 65 years with a history of chronic disease.

Background: Curcumin, a compound derived from the root of the Curcuma longa, has been confirmed as an anticancer, chemoprotective, and gene/protein regulatory agent. Nanoformulation of curcumin has been developed to increase its targeting efficiency, solubility, controlled release, and physical and chemical stability.

Objectives: This study investigated the effect of new nano-type curcumin, oleic acid-derived dendrosome (OA400 nanoparticles), on the expression of E6 and E7 human papillomavirus oncogenes and P53 and Rb factors in the HeLa cell line. After preparing nano-curcumin by mixing OA400 nano-carrier and curcumin, its effect was considered on the human cervical cancer cell line (HeLa cell line RRID: CVCL_003) and normal fibroblast cells.

Methods: MTT assay and flow cytometry were used to evaluate cell viability and apoptosis. Furthermore, real-time RT-PCR and western blot analyses assessed RNA and protein expression of E6, E7, P53, and Rb. Statistical analyses were performed by GraphPad Prism 7 software.

Results: The nanoformulation of curcumin could reduce the expression of E6 and E7 oncogenes and increase P53 and Rb tumor suppressors in HeLa cancerous cells at 15 μM concentration; however, it had no significant effect on the viability of normal fibroblast cells. On the other hand, curcumin altered the expression of these genes at a 50-μM concentration. Gene and protein expression analysis indicated the up-regulation of P53 and Rb factors and the down-regulation of E6 and E7 under the influence of nano-curcumin treatment more than curcumin.

Conclusions: These data indicate the potential of curcumin-loaded OA400 nanoparticles to be considered as a treatment option in cervical cancer investigations.

Background: Drug resistance in breast cancer is an unsolved problem in treating patients. It has been recently discussed that lysosomes contribute to the invasion and angiogenesis of cancer cells. There is evidence that lysosomes can also cause multi-drug resistance. We analyzed this emerging concept in breast cancer through computational and systems biology approaches.

Objectives: We aimed to identify the key lysosome-related genes associated with drug-resistant breast cancer.

Methods: All genes contributing to the structure and function of lysosomes were inquired through the Human Lysosome Gene Database. The prioritized top 51 genes from the provided lists of Endeavour, ToppGene, and GPSy as prioritization tools were selected. All lysosomal genes and 12 breast cancer-related genes aligned to identify the most similar genes to breast cancer-related genes. Different centralities were applied to score each human protein to calculate the most central lysosomal genes in the human protein-protein interaction (PPI) network. Common genes were extracted from the results of the mentioned methods as a selected gene set. For Gene Ontology enrichment, the selected gene set was analyzed by WebGestalt, DAVID, and KOBAS. The PPI network was constructed via the STRING database. The PPI network was analyzed utilizing Cytoscape for topology network interaction and CytoHubba to extract hub genes.

Results: Based on biological studies, literature reviews, and comparing all mentioned analyzing methods, six genes were introduced as essential in breast cancer. This computational approach to all lysosome-related genes suggested that candidate genes include PRF1, TLR9, CLTC, GJA1, AP3B1, and RPTOR. The analyses of these six genes suggest that they may have a crucial role in breast cancer development, which has rarely been evaluated. These genes have a potential therapeutic implication for new drug discovery for chemo-resistant breast cancer.

Conclusions: The present work focused on all the functional and structural lysosome-related genes associated with breast cancer. It revealed the top six lysosome hub genes that might serve as therapeutic targets in drug-resistant breast cancer. Since these genes play a pivotal role in the structure and function of lysosomes, targeting them can effectively overcome drug resistance.

Background: Overexpression of programmed cell death ligand 1 (PD-L1) in tumor cells and subsequent interaction with the programmed cell death protein 1 (PD-1) in tumor-infiltrating T cells cause an immune evasion of the tumor from cytotoxic T-cells. Therefore, inhibiting such interaction by a recombinant PD-1 can hinder tumor growth and extend the survival rate.

Methods: The mouse extracellular domain of PD-1 (mPD-1) was expressed in E. coli BL21 (DE3) strain and purified using nickel affinity chromatography. The binding ability of the purified protein to human PD-L1 was studied using ELISA. Finally, the tumor-bearing mice were used to evaluate the potential antitumor effect.

Results: The recombinant mPD-1 showed a significant binding capacity to human PD-L1 at the molecular level. The tumor size significantly decreased in the tumor-bearing mice after the intra-tumoral injections of mPD-1. Moreover, the survival rate increased significantly after eight weeks of monitoring. The histopathology revealed the necrosis in the tumor tissue of the control group compared to the mPD-1 received mice.

Conclusions: Our outcomes propose that interaction blockade between PD-1 and PD-L1 is a promising approach for targeted tumor therapy.

Background: Polypharmacy is a significant patient safety concern.

Objectives: This study aims to estimate the prevalence of polypharmacy, its continuity and associated factors, and common medication classes among a large outpatient population in East Azerbaijan province, Iran.

Methods: A retrospective prescription data analysis was performed. The cohort included all ≥ 20 years old subjects with at least one prescription filled during the main three-month study period (2020 March 1 - 2020 May 31). Polypharmacy was defined as being exposed to more than four different medications during the main study period, and continuous polypharmacy was defined as being exposed to more than four medications during both the main study period and follow-up period (2020 October 1 - 2020 December 31). The frequency and prevalence of polypharmacy, along with predictive factors, were estimated. We performed multivariate logistic regression and estimated odds ratios (ORs) to investigate the risk factors for polypharmacy.

Results: 307,820 patients included (mean age 49.8 years, 62.9% female, mean drug use 3.7 (SD = 2.6). Polypharmacy was observed in 28.3% (CI: 28.1 - 28.4), of which 36.6% experienced continuous polypharmacy. The odds of being exposed to polypharmacy increased with being female, increasing age, and exposure to chronic conditions. The groups of medications most utilized by polypharmacy patients were those indicated for gastro-esophageal reflux diseases, beta-blocking agents, antidepressants, blood glucose-lowering drugs, and antithrombotic agents.

Conclusions: Strategies should be formulated to inform healthcare policymakers and providers about the magnitude of the polypharmacy phenomenon, associated factors, and the common medication classes involved.

Background: Coronavirus disease 2019 (COVID-19) affects the pediatric population.

Objectives: Due to limited data, this study aimed to evaluate the safety and efficacy of favipiravir in the hospitalized pediatric population diagnosed with COVID-19.

Methods: The present retrospective cohort study was conducted on pediatric patients aged 1 - 18 years with a diagnosis of COVID-19 admitted to Mofid Children's Hospital, Tehran, Iran. Favipiravir was administrated at a dose of 60 mg/kg/day (max: 3200 mg/day) on the first day and then 23 mg/kg/day (max: 1200 mg/day) for 7 to 14 days. The patients were evaluated regarding the need for invasive mechanical ventilation, intensive care unit admission, duration of hospital stay, and mortality. Safety was measured by the occurrence of related adverse drug reactions (ADRs).

Results: A total of 95 patients were included in the study. Favipiravir was administered to 25 patients. The need for invasive mechanical ventilation was reported in 4 (16.00%) and 11 (15.71%) patients in the favipiravir and control groups, respectively (P = 1.000). The median duration of hospital stays was significantly higher in patients who received favipiravir than in the controls (P = 0.002). No difference was observed in the mortality rate (P = 0.695). The ADRs, including decreased appetite, hypotension, and chest pain, were more prevalent in patients who received favipiravir than in the controls (P < 0.05).

Conclusions: The administration of favipiravir in the pediatric population is associated with higher ADR occurrence with no positive effect on the need for invasive mechanical ventilation, hospital stay, and mortality. Further randomized controlled trials are necessary for better judgment.

Background: Since the incidence of food adulteration is rising, finding a rapid, accurate, precise, low-cost, user-friendly, high-throughput, ruggedized, and ideally portable method is valuable to combat food fraud. Near-infrared spectroscopy (NIRS), in combination with a chemometrics-based approach, allows potentially rapid, frequent, and in situ measurements in supply chains.

Methods: This study focused on the feasibility of a benchtop Fourier-transformation-NIRS apparatus (FT-NIRS, 1000 - 2500 nm) and a portable short wave NIRS device (SW-NIRS, 740 - 1070 nm) for the discrimination of genuine and citric acid-adulterated lime juice samples in a cost-effective manner following chemometrics study.

Results: Principal component analysis (PCA) of the spectral data resulted in a noticeable distinction between genuine and adulterated samples. Wavelengths between 1100 - 1400 nm and ‎‎1550 - 1900 nm were found to be more important for the discrimination of samples for the benchtop FT-NIRS data, while variables between 950 - 1050 nm contributed significantly to the discrimination of samples based on the portable SW-NIRS data. Following partial least squares discriminant analysis (PLS-DA) as a discriminant model, standard normal variate (SNV) or multiplicative scatter correction (MSC) transformation of benchtop FT-NIRS data and SNV in combination with the second derivative transformation of portable SW-NIRS data on the training set delivered equal accuracy (94%) in the prediction of the test set. In the soft independent modeling of class analogy (SIMCA) as a class-modeling approach, the overall performances of generated models on the auto-scaled data were 98% and 94.5% for benchtop FT-NIRS and portable SW-NIRS, respectively.

Conclusions: As a proof of concept, NIRS technology coupled with appropriate ‎multivariate classification models enables fast detection of citric acid-adulterated ‎lime juices. In addition, the promising results of portable SW-NIRS combined with SIMCA indicated its use as a screening tool for on-site analysis of lime juices at various stages of the food supply chain.

Background: Colorectal cancer (CRC) is the most frequent death-causing disease in the world. The Trametes versicolor mushroom, a traditional Chinese medicine, has been used as anti-cancer medicine with long history. Its cultured mycelia extracts, namely polysaccharide peptide (PSP) as the major active component in Trametes versicolor, is widely used in eastern countries to stimulate the immune system and treat deadly cancers, including CRC.

Methods: This study aimed to explore the mechanism through which PSP inhibits CRC cells proliferation. In vitro, cell proliferation and cytotoxicity of PSP were assessed using human CRC cell lines (HCT116 and HT29). The real-time polymerase chain reaction (PCR), western blot, and immunofluorescence methods were used to examine the expression of epidermal growth factor receptor (EGFR), programmed cell death-ligand 1 (PD-L1), activator of transcription 3 (STAT3), c-Jun, and NF-κB in the PSP treated CRC cells. Human peripheral blood mononuclear cells (PBMC), which were activated with CD3/CD28/CD2 T cell activator and interleukin 2 (IL-2), were co-cultured with HCT116, which was pre-treated with PSP to reduce PD-L1 expression. The synergic effect of T-cells killing was evaluated using the terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) method.

Results: Polysaccharide peptide significantly inhibited proliferation of HCT116 and HT29 cell line in vitro. Polysaccharide peptide strongly reduced the expression and phosphorylation level of EGFR. In addition, PSP pretreatment significantly decreased the expression of downstream molecules PD-L1 and EGFR signaling pathways (c-Jun and STAT3) in HCT116. Polysaccharide peptide pretreatment enhanced the T-cells killing effect induced by co-culture PBMC on HCT116 cells.

Conclusions: Polysaccharide peptide may be used as a prophylactic and therapeutic agent against CRC via down-regulating PD-L1 and EGFR signaling pathway.