Advanced pharmaceutical bulletin最新文献

Modern science has been transformed by open access (OA) publishing levied a significant economic burden on the authors. This article analyzes the discrepancies among OA publication fees in pharmacology, toxicology, and pharmaceutics. The observations comprise 160 OA journals and their corresponding Q ranking, SJR, H index, impact factor, country, and cost of publication. The OA fees were found to depend on the quality matrices, which was unexpected. Differences in OA fees raise ethical questions as OA fees are meant to cover the publication charges by the publishers or generate more revenues by taking advantage of the authors' temptation to publish in high-impact journals. Despite our findings being based on limited sample size and belonging to a particular field (pharmacy), it will shed considerable light on the issue of discrepancies among APCs charged by OA journals.

Purpose: Exosomes are natural nanoparticles that participate in intercellular communication through molecular transport. Recently, due to their membrane vesicular structure and surface proteins, exosomes have been used extensively in the research field of drug delivery. Osteoporosis is an inflammation in which the cellular balance of bone tissue is disturbed that reduces bone density and making bone prone to abnormal fractures with small amount of force. Utilizing estrogen is one of the main therapeutic strategies for osteoporosis. Despite the positive effects of estrogen on bone tissue, changes in the natural estrogen levels of the body can cause a number of diseases such as different types of cancer. Therefore, designing a therapeutic system which controls more accurate tissue targeting of estrogen seems to be a rational and promising practical approach.

Methods: In this study, bone marrow mesenchymal stem cells (BMMSCs)-derived exosomes were loaded by estradiol using two different methods of drug loading, namely incubation and sonication methods and then the survival effects of the drug loaded exosomes on BMMSCs was investigated.

Results: Examination of size, shape, and surface factors of exosomes in different states (pure exosomes and drug-loaded exosomes) showed that the round morphology of exosomes was preserved in all conditions. However, the particles size increased significantly when loaded by sonication method. The increased survival of BMMSCs was noted with estradiol-loaded exosomes when compared to the control group.

Conclusion: The results suggest that estradiol-loaded exosomes have potential to be used as nano-drug carriers in the treatment of osteoporosis.

Purpose: The purpose of this study was to develop a robust and externally predictive in silico QSAR-neural network model for predicting plasma protein binding of drugs. This model aims to enhance drug discovery processes by reducing the need for chemical synthesis and extensive laboratory testing.

Methods: A dataset of 277 drugs was used to develop the QSAR-neural network model. The model was constructed using a Filter method to select 55 molecular descriptors. The validation set's external accuracy was assessed through the predictive squared correlation coefficient Q2 and the root mean squared error (RMSE).

Results: The developed QSAR-neural network model demonstrated robustness and good applicability domain. The external accuracy of the validation set was high, with a predictive squared correlation coefficient Q2 of 0.966 and a root mean squared error (RMSE) of 0.063. Comparatively, this model outperformed previously published models in the literature.

Conclusion: The study successfully developed an advanced QSAR-neural network model capable of predicting plasma protein binding in human plasma for a diverse set of 277 drugs. This model's accuracy and robustness make it a valuable tool in drug discovery, potentially reducing the need for resource-intensive chemical synthesis and laboratory testing.

Purpose: Medical usage of L-asparaginase (ASNase), the first-line of acute lymphoblastic leukemia treatment, is linked to allergic responses and toxicities, which necessitates the development of new bio-better ASNases. The aim of the current study was in silico design of a novel ASNase with predicted improved enzymatic properties using strategies encompassing sequence-function analysis of known ASNase mutants. Additionally, current study aimed to show that the new enzyme is active.

Methods: Based on 21 experimentally reported mutations for ASNase, a virtual library of mutated enzymes with all 7546 possible combinations of up to 4 mutations was generated. Three-dimensional models of proposed mutant enzymes were built and their in silico stabilities were calculated. The most promising mutant was selected for preparing a genetic construct suitable for expression of the designed ASNase in bacterial cells.

Results: Computational study predicted that Y176F/S241C double mutation of Escherichia coli ASNase may increase its folding stability. The designed ASNase was expressed in two different E. coli strains (Origami B(DE3) and BL21(DE3)pLysS) and then the soluble fractions prepared from the cell lysates of the host cells were used in enzyme activity assay. Results showed that enzyme activity of soluble fraction from Origami (95.4 ± 7.5 IU/0.1 mL) was four times higher than that of soluble fraction from pLysS (25.8 ± 2.5 IU/0.1 mL).

Conclusion: A novel functional double mutant ASNase with predicted improved enzymatic properties was designed and produced in E. coli. The results of the current study suggest a great commercial potential for the identified enzyme in pharmaceutical and industrial applications.

Purpose: Eliminating cancer stem cells (CSCs) is a challenge because of their enhanced resistance to anti-cancer drugs. Vitamin C, which is insufficient in patients with higher stages of cancer, has been gaining attention as a potential treatment for human malignancies. Hence this study aimed to analyze the effect of high-dose vitamin C treatment on the gene expression level of HIF-1α, NF-κB1, BAX, and DNMT1 in the MCF7 cells undergoing hypoxia, as an inducer of CSCs characteristics. As a result, vitamin C could be possibly used as a promising therapeutic adjuvant.

Methods: Here we first analyzed the breast CSC population alteration in MCF7 cells following hypoxia induction. Then, we evaluated the impact of vitamin C treatment on the gene expression level of four stemness-related genes in hypoxic MCF7 cells.

Results: Our results indicate that vitamin C could reduce proliferation and stemness states in CSCs possibly by induction of apoptotic markers such as BAX, along with attenuating stemness markers, including NF-κB1, and DNMT1 gene expressions.

Conclusion: According to our findings, vitamin C administration would become a new approach to avoiding the stimulation of CSCs during cancer therapies.

Several vaccine-induced thrombotic thrombocytopenia syndrome (VITTS) cases have been reported after the ChAdOx1 nCov-19 vaccination. The current study systematically reviewed the reported post-ChAdOx1 nCoV-19 vaccination thrombotic thrombocytopenia cases. Their laboratory and clinical features, as well as the diagnostic and therapeutic measures, were investigated. Online databases were searched until 25 August 2021. Studies reporting post-ChAdOx1 nCov-19 vaccination thrombotic thrombocytopenia syndrome (TTS) were included. Overall, 167 cases (21-77 years old) from 53 publications were included showing a female dominance of 1.75 times. About 85% of the cases exhibited the primary symptoms within the first two weeks post-vaccination. Headache was the most common initial symptom (>44.2%), and hemorrhage/thrombotic problems (22.46%), as well as discoordination/weakness/numbness/ hemiparesis/cyanotic toes (19.6%), were the most prevalent uncommon initial symptoms. Prothrombin time (PT), D-dimers, and C-reactive protein were the most remarkable increased laboratory parameters in 50.6%, 99.1%, and 55.6% of cases, respectively. In comparison, platelet and fibrinogen were the most remarkable decreased laboratory parameters in 92.7% and 50.5% of cases, respectively. Most VITT cases presented with cerebral venous thrombosis/cerebral venous sinus thrombosis, supraventricular tachycardia, transverse sinus/cerebral thrombosis, pulmonary embolism, and cerebral hemorrhage. Anti-PF4 antibody measurement through immunoassays and functional assays were positive in 86.2% and 73% of cases, respectively. About 31% of the cases died. Early diagnosis and proper therapeutic measures are important in ChAdOx1 nCov-19 vaccine-induced VITTS patients. Therefore, experts are recommended to know the corresponding clinical and laboratory features, as well as diagnostic methods. Elucidation of the pathophysiologic mechanism of ChAdOx1 nCov-19 vaccine-induced TTS deserves further investigation.

Purpose: Pennyroyal is a species of the Lamiaceae family with potent anti-cancer and antioxidant properties. Combining this antioxidant with chemotherapeutic agents enhances the effectiveness of these agents by inducing more apoptosis in cancerous cells.

Methods: Here, methotrexate (MTX) combined with pennyroyal oil based on PEGylated nanostructured lipid carriers (NLCs) was assessed. These nanoparticles were physiochemically characterized, and their anti-cancer effects and targeting efficiency were investigated on the folate receptor-positive human breast cancer cell line (MCF-7) and negative human alveolar basal epithelial cells (A549).

Results: Results showed a mean size of 97.4 ± 12.1 nm for non-targeted PEGylated NLCs and 220.4 ± 11.4 nm for targeted PEGylated NLCs, with an almost small size distribution assessed by TEM imaging. Furthermore, in vitro molecular anti-cancer activity investigations showed that pennyroyal-NLCs and pennyroyal-NLCs/MTX activate the apoptosis and autophagy pathway by changing their related mRNA expression levels. Furthermore, in vitro cellular studies showed that these changes in the level of gene expression could lead to a rise in apoptosis rate from 15.6 ± 8.1 to 25.0 ± 3.2 (P<0.05) for the MCF-7 cells treated with pennyroyal-NLCs and pennyroyal-NLCs/MTX, respectively. Autophagy and reactive oxygen species (ROS) cellular evaluation indicated that treating the cells with pennyroyal-NLCs and pennyroyal-NLCs/MTX could significantly increase their intensity in these cells.

Conclusion: Our results present a new NLCs-based approach to enhance the delivery of pennyroyal and MTX to cancerous breast tissues.

The incidence rate of melanoma is dramatically increasing worldwide, raising it to the fifth most common cancer in men and the sixth in women currently. Resistance generally occurs to the agents used in chemotherapy; besides their high toxicity destroys the normal cells. This study reviewed a detailed summary of the structure, advantages, and disadvantages of nanotechnology-based drug delivery systems in the treatment of melanoma, as well as some nanocarrier applications in animal models or clinical studies. Respective databases were searched for the target keywords and 93 articles were reviewed and discussed. A close study of the liposomes, niosomes, transferosomes, ethosomes, transethosomes, cubosomes, dendrimers, cyclodextrins, solid lipid nanoparticles, and carbon nanotubes (CNTs) was conducted. It was found that these nanocarriers could inhibit metastasis and migration of melanoma cells and decrease cell viability. Conclusively, some nanocarriers like liposomes, niosomes, and transferosomes have been discussed as superior to conventional therapies for melanoma treatment.

Infection with SARS-CoV-2 is a growing concern to the global well-being of the public at present. Different amino acid mutations alter the biological and epidemiological characteristics, as well as immune resistance of SARS-CoV-2. The virus-induced pulmonary impairment and inflammatory cytokine storm are directly related to its clinical manifestations. But, the fundamental mechanisms of inflammatory responses are found to be the reason for the death of immune cells which render the host immune system failure. Apoptosis of immune cells is one of the most common forms of programmed cell death induced by the virus for its survival and virulence property. ORF3a, a SARS-CoV-2 accessory viral protein, induces apoptosis in host cells and suppress the defense mechanism. This suggests, inhibiting SARS-CoV-2 ORF3a protein is a good therapeutic strategy for the treatment in COVID-19 infection by promoting the host immune defense mechanism.

Purpose: In this study, we prepared inhalable buserelin microparticles using the spray freeze-drying (SFD) method for pulmonary drug delivery. Raffinose as a cryoprotectant carrier was combined with two levels of five different cyclodextrins (CDs) and then processed by SFD.

Methods: Dry powder diameters were evaluated by laser light scattering and morphology was determined by scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis were utilized for the determination of crystalline structures. The aerodynamic properties of the spray freeze-dried powders were evaluated by twin stage impinger (TSI) and the stability of prepared samples was assessed under normal and accelerated conditions.

Results: The prepared powders were mostly porous spheres and the size of microparticles ranged from 9.08 to 13.53 μm, which are suitable as spray-freeze dried particles. All formulations showed amorphous structure confirmed by DSC and XRD. The aerosolization performance of the formulation containing buserelin, raffinose and 5% beta-cyclodextrin (β-CD), was the highest and its fine particle fraction (FPF) was 69.38%. The more circular and separated structures were observed in higher concentrations of CDs, which were compatible with FPFs. The highest stability was obtained in the formulation containing hydroxypropyl beta-cyclodextrin (HP-β-16. CD) 5%. On the contrary, sulfobutylether beta-cyclodextrin (SBE-β-CD) 5% bearing particles showed the least stability.

Conclusion: By adjusting the type and ratio of CDs in the presence of raffinose, the prepared formulations could effectively enhance the aerosolization and stability of buserelin. Therefore, they can be proposed as a suitable career for lung drug delivery.