Solubility and thermodynamics of mesalazine in aqueous mixtures of poly ethylene glycol 200/600 at 293.2-313.2K.

In this study, the solubility of mesalazine was investigated in binary solvent mixtures of poly ethylene glycols 200/600 and water at temperatures ranging from 293.2K to 313.2K. The solubility of mesalazine was determined using a shake-flask method, and its concentrations were measured using a UV-Vis spectrophotometer. The obtained solubility data were analyzed using mathematical models including the van't Hoff, Jouyban-Acree, Jouyban-Acree-van't Hoff, mixture response surface, and modified Wilson models. The experimental data obtained for mesalazine dissolution encompassed various thermodynamic properties, including ΔG°, ΔH°, ΔS°, and TΔS°. These properties offer valuable insights into the energetic aspects of the dissolution process and were calculated based on the van't Hoff equation.

Applications of Exhaled Breath Condensate Analysis for Drug Monitoring and Bioequivalence Study of Inhaled Drugs.

The exhaled breath condensate (EBC) presents a simple and non-invasive alternative approach for bioequivalence assessments and therapeutic drug monitoring of inhaled drugs. EBC better represents the drug at the site of action and eliminates the possibility of the contribution of a swallowed portion of the dose when systemic bioavailability is used for assessment. This review summarizes the recently reported analytical methods for the quantification of drugs in EBC. It also discusses the difficulties in the bioequivalence evaluation criteria of generic orally inhaled drug products suggested by various regulatory agencies that may be eliminated using the EBC analysis approach.

Corrigendum: Applications of exhaled breath condensate analysis for drug monitoring and bioequivalence study of inhaled drugs.

[This corrects the article DOI: 10.18433/jpps33121.].

Analysis and identification of drug similarity through drug side effects and indications data.

BACKGROUND: The measurement of drug similarity has many potential applications for assessing drug therapy similarity, patient similarity, and the success of treatment modalities. To date, a family of computational methods has been employed to predict drug-drug similarity. Here, we announce a computational method for measuring drug-drug similarity based on drug indications and side effects. METHODS: The model was applied for 2997 drugs in the side effects category and 1437 drugs in the indications category. The corresponding binary vectors were built to determine the Drug-drug similarity for each drug. Various similarity measures were conducted to discover drug-drug similarity. RESULTS: Among the examined similarity methods, the Jaccard similarity measure was the best in overall performance results. In total, 5,521,272 potential drug pair's similarities were studied in this research. The offered model was able to predict 3,948,378 potential similarities. CONCLUSION: Based on these results, we propose the current method as a robust, simple, and quick approach to identifying drug similarity.

Review of Pharmaceutical Applications of Diethylene Glycol Monoethyl Ether.

Diethylene glycol monoethyl ether (DEGME) is a hydroalcoholic solvent that gained tremendous attention in the cosmetics, food, nanoformulations, and pharmaceutical industries. Due to its physicochemical features, it has been widely used as a penetration enhancer, surfactant, and solubilizer. Among numerous tradenames defined for DEGME -- Carbitol® (by Dow Chemical Co., USA), and Transcutol® HP, CG, and P. (by Gattefossé Co., France) -- are known to be employed in pharmaceutical industries. Transcutol® CG is utilized only in cosmetics; however, Transcutol® P and Carbitol® are both used in various pharmaceutical topical dosage forms such as creams, gels, etc. Additionally, Transcutol® HP is used in all administration routes. In view of this, the application of DEGME is highlighted in the areas of industry and pharmaceutical sciences. Moreover, in this review the prominent characteristics, pharmacokinetics, and toxicity of DEGME are examined and it is suggested that DEGME is a promising solvent/solubilizer with comparable assignments to other conventional excipients.

Targeted combined therapy in 2D and 3D cultured MCF-7 cells using metformin and erlotinib-loaded mesoporous silica magnetic nanoparticles.

AIM: This research aims to develop potential therapeutic nanostructures (NSs) encapsulating metformin (MET) and erlotinib (ER) for combinational therapy in breast cancer. METHODS: The ER and MET, both were loaded on mesoporous silica magnetic nanoparticles conjugated with polyethylene glycol and methotrexate to achieve targeted NSs. The developed NSs were characterised using SEM, DLS, and FTIR. Afterward, MTT, Trypan blue, and DNA extraction assays were operated for biological evaluations in the 2D and 3D MCF-7 cells. RESULTS: Physicochemical approaches indicated the mean diameter of 69.4 nm ± 9.5 (PDI = 0.64), and neutral charge (2 mv) for the developed NSs. MET and ER-loaded NSs exhibited 62.56% ± 4.41 and 67.73% ± 3.03 drug release amount in pH = 5.4, respectively. MTT assay revealed that ER- and MET-loaded NSs had less metabolic activity (≈ 20%) in comparison with non-targeted NSs. CONCLUSION: Overall, our combined ER and MET-loaded targeted NSs result in a synergistic inhibitory impact on MCF-7 cells.

Piperacillin Encapsulation in Nanoliposomes Using Modified Freeze-Drying of a Monophase Solution Method: Preparation, Characterization and In Vitro Antibacterial Activity.

Piperacillin (Pip) is a broad spectrum ß-lactam against most Gram-positive and Gram-negative aerobic and anaerobic bacteria. However, bacterial resistance restricts its benefits for the treatment of infectious diseases. Recently, nanoliposomal systems have been investigated as encouraging strategies to address this issue owing to their immense potential. We aimed to encapsulate Pip in liposomal nanoparticles and study their antibacterial activities in vitro against Pseudomonas aeruginosa (P. aeruginosa). Different liposomes were prepared based on the freeze-drying of a monophase solution method. Then, they were characterized in terms of size, zeta potential, polydispersity-index, and morphology. For further analysis, spectra of ATR-FTIR and XRD were taken for liposomal Pip. Encapsulation efficiency (EE) was determined via agar diffusion assay. Also, minimum inhibitory concentrations (MICs) were investigated by the standard broth macro-dilution method. The liposomes were from 100.9 to 444.13 nm with z-potential of - 30.70 to - 10.57 mV. EE of the selected formulation was 53.1%. TEM results showed that the liposomes were nanosized and almost spherical. ATR-FTIR results confirmed the full encapsulation of Pip in nanoliposomes. The X-ray pattern indicated that the liposomal Pip was amorphous. The MIC (10.6 µg/ml) of the nanoliposomal Pip against P. aeruginosa was one-half of the MIC (21.25 µg/ml) of free Pip for the same organisms. Considering four aspects (nanosized liposomes, no need for sterilization, suitable EE and enhanced antibacterial effects), this preparation method seems promising and may be used to overcome the bacterial resistance relative to Pip.

Utilizing a graphene quantum dot/hydrogel nanocomposite for determination of cisplatin in urine samples.

Currently, the growth and development of cancer are rising in the world, and as a result, the use of anticancer drugs such as cisplatin has also increased. Considering that the therapeutic index of anticancer drugs is low, it is essential to design and develop an accurate and correct method to analyze and determine the concentration of anticancer drugs in the biological samples. In this study, graphene quantum dots/hydrogel nanocomposite was used to determine cisplatin concentration in urine samples. A three-dimensional network of polyvinyl alcohol hydrogel was composited with graphene quantum dots and used as a probe for the determination of cisplatin. The morphology and characterization of the probe were studied using high-resolution transmission electron microscopy, dynamic light scattering, energy-dispersive X-ray spectroscopy, and Fourier transform infrared spectroscopy. This platform showed a linear calibration curve in the range from 4.3 to 25.0 ng mL-1 with a detection limit of 1.2 ng mL-1. The relative intra- and inter-day standard deviations of the probe for the determination of cisplatin were 1.8% and 3.6% (n = 5), respectively. The validated method was used for determination of cisplatin in urine samples of patients receiving this medication with acceptable results and good recoveries.

A cross-sectional study on metoprolol concentrations in various biological samples and their inter-correlations.

BACKGROUND: Concentrations of metoprolol in exhaled breath condensate (EBC) have not been investigated. Herein, we aim to determine the metoprolol levels in EBC, plasma, and urine samples. METHODS: Biological samples were collected from 39 patients receiving metoprolol. Metoprolol was determined using liquid chromatography mass spectrometery. The obtained metoprolol levels in biological fluids were investigated for possible inter-correlations. RESULTS: Acceptable linearity was obtained with coefficient of determinations equal to 0.9998, 0.9941, and 0.9963 for EBC, plasma, and urine samples, respectively. The calibration curves were linear in the ranges of 0.6-500, 0.4-500, and 0.7-10,000 µg·L- 1 regarding EBC, plasma, and urine samples, respectively. The detection and quantification limits were (0.18, 0.12, and 0.21 µg·L- 1) and (0.60, 0.40, and 0.70 µg·L- 1) for EBC, plasma, and urine samples, respectively. The relative standard deviations for the intra- and inter-day replications were obtained between 5.2 and 6.1 and 3.3-4.6%, respectively. The obtained mean metoprolol levels in EBC, plasma, and urine samples of 39 patients were 5.35, 70.76, and 1943.1 µg·L- 1. There were correlations between daily dose and plasma and urinary concentrations of metoprolol in the investigated samples, whereas no significant correlation was observed for daily dose and EBC levels. The correlation among plasma-urine levels was significant, however, the non-significant correlation was obtained between plasma and EBC concentrations. CONCLUSION: Metoprolol levels varied widely due to the metabolic pattern of the Azeri population, different dosages received by the patients, formulation effects, age, sex, and interactions with the co-administered drugs. A poor correlation of EBC-plasma concentrations and a significant correlation of plasma-urine concentrations were observed. Further investigations are required to provide the updated services to personalized medicine departments.

COVID -19: From the Molecular Mechanisms to Treatment.

The 2019 novel coronavirus (SARS-CoV-2) causes severe pneumonia called COVID-19 and leads to severe acute respiratory syndrome with a high mortality rate. The SARS-CoV-2 virus in the human body leads to jumpstarting immune reactions and multi-organ inflammation, which has poorer outcomes in the presence of predisposing conditions, including hypertension, dyslipidemia, dysglycemia, abnormal adiposity, and even endothelial dysfunction via biomolecular mechanisms. In addition, leucopenia, hypoxemia, and high levels of both cytokines and chemokines in the acute phase of this disease, as well as some abnormalities in chest CT images, were reported in most patients. The spike protein in SARS-CoV-2, the primary cell surface protein, helps the virus anchor and enter the human host cells. Additionally, new mutations have mainly happened for spike protein, which has promoted the infection's transmissibility and severity, which may influence manufactured vaccines' efficacy. The exact mechanisms of the pathogenesis, besides molecular aspects of COVID-19 related to the disease stages, are not well known. The altered molecular functions in the case of immune responses, including T CD4+, CD8+, and NK cells, besides the overactivity in other components and outstanding factors in cytokines like interleukin-2, were involved in severe cases of SARS-CoV-2. Accordingly, it is highly needed to identify the SARSCoV-2 biomolecular characteristics to help identify the pathogenesis of COVID-19. This study aimed to investigate the biomolecular aspects of SARSCoV-2 infection, focusing on novel SARS-CoV-2 variants and their effects on vaccine efficacy.

Cell homing strategy as a promising approach to the vitality of pulp-dentin complexes in endodontic therapy: focus on potential biomaterials.

INTRODUCTION: Over the last two decades, an increasing body of research suggests that well-designed biomaterials can attract resident stem cells to injured areas and control their behaviors and activities to encourage tissue regeneration. Fabricated biomaterials can enhance cell recruitment, multiplication, and transformation while also acting as a delivery system for targeted cells. These capabilities might play a role in their ability to promote tooth regeneration. AREAS COVERED: This review aims to introduce the various materials used in endodontics. The potential of biomaterial-based approaches involved in cell homing for endodontics is also discussed. EXPERT OPINION: Applying the cell homing technique in restorative dentistry can affect various aspects of healthcare, industry, economy, and science. Biomaterial scaffolds can be used to encapsulate cells or for structural replacements. Also, both cell transplantation and cell homing are legitimate scientific procedures in endodontic therapy. Although the suggested biomaterials and procedures may hold promise for future dental pulp tissue regeneration, tooth structure's complexity and multicellular interconnections lead to significant problems that need to be overcome before any clinical trial.

Folate receptor-mediated delivery of 1-MDT-loaded mesoporous silica magnetic nanoparticles to target breast cancer cells.

Aims: The efficiency of mesoporous silica magnetic nanoparticles (MSMNP) as a targeted drug-delivery system was investigated. Methods: The superparamagnetic iron oxide nanoparticles (NP) were synthesized, coated with mesoporous silica and conjugated with polyethylene glycol and methotrexate. Next, 1-methyl-D-tryptophan was loaded into the prepared nanosystems (NS). They were characterized using transmission electron microscopy, scanning electron microscopy, dynamic light scattering, vibrating sample magnetometer, x-ray powder diffraction, Fourier transform-infrared spectroscopy and the Brunauer-Emmett-Teller method and their biological impacts on breast cancer cells were evaluated. Results: The prepared NSs displayed suitable properties and showed enhanced internalization by folate-receptor-expressing cells, exerting efficient cytotoxicity, which was further enhanced by the near-infrared radiation irradiation. Conclusion: On the basis of our findings, the engineered NS is a promising multifunctional nanomedicine/theranostic for solid tumors.

Recent advances in breast cancer immunotherapy: The promising impact of nanomedicines.

Breast cancer (BC) is one of the prevalent cancers among women. Generally, the treatment of BC is mostly based on several prominent strategies, including chemotherapy, surgery, endocrine therapy, molecular targeted therapy, and radiation. Owing to the growing knowledge about the complexity of BC pathobiology, immunotherapy as a promising treatment modality has substantially improved the patients' care in the clinic. Immunotherapy is used to harness the patient's immune system to recognize and battle devious cancer cells. As a novel therapy approach, this emerging strategy targets the key molecular entities of tumor tissue. To achieve maximal therapeutic impacts, the dynamic interplay between cancer and immune cells needs to be fully comprehended. The key molecular machinery of solid tumors can be targeted by nanoscale immunomedicines. While discussing the potential biomarkers involved in the initiation and progression of BC, we aimed to provide comprehensive insights into the immunotherapy and articulate the recent advances in terms of the therapeutic strategies used to control this disease, including immune checkpoint inhibitors, vaccines, chimeric antigen receptor T cells therapy, and nanomedicines.

Stimuli-responsive graphene oxide and methotrexate-loaded magnetic nanoparticles for breast cancer-targeted therapy.

Aim: Nanocomposites of graphene oxide (GO) loaded with PEGylated superparamagnetic iron oxide nanoparticles and grafted with methotrexate and stimuli-responsive linkers (GO-SPION-MTX) were developed for photothermal and chemotherapy of breast cancer. Methods: PEGylated SPIONs were synthesized and conjugated with chemotherapeutic targeting agent MTX, which were then loaded on GO to prepare GO-SPION-MTX nanocomposites. To evaluate the photothermal effect of the nanocomposites, they were examined in breast cancer cell lines with low doses of near-infrared (NIR) laser radiation with/without acetazolamide. Results: The GO-SPION-MTX nanocomposites were found to be internalized by the folate-receptor-positive cancer cells and induce high cytotoxicity on exposure to NIR laser rays. Conclusion: Our findings suggest that the GO-SPION-MTX nanocomposite can potentially be used as a multimodal nanomedicine/theranostic against breast cancer.

Graphene-based multifunctional nanosystems for simultaneous detection and treatment of breast cancer.

Breast cancer is one of the most life-threatening malignancies with high mortality among women. Chemotherapy, radiotherapy, surgical operation, and combination therapy are commonly applied modalities in breast cancer therapy. However, the full treatment of the disease is often failed because of the formation of a permissive milieu, so-called tumor microenvironment (TME). In such a setting, immunosurveillance is impaired and high-pressure tumor interstitial fluid resists drug penetration due to the creation of irregular tumor microvasculature, the initiation of drug resistance mechanisms, the emergence of undesired side effects, and relapse of the disease even after a vigorous treatment. To tackle these pitfalls, smart multifunctional nanosystems (NSs) have been developed based on passive and active targeting mechanisms. Of various NSs, graphene-based nanosystems (GrNSs) offer unique physicochemical features, including functionalization with various targeting and imaging ligands, offering photothermal and photodynamic therapy (PTT and PDT) potentials combined with chemotherapy of the loaded drugs. Multimodal GrNSs, to be transformed into precision medicine, demand rationalized preclinical and clinical studies to examine their pharmacokinetics and pharmacodynamics (PD) properties together with their behaviors in TME. For a successful transformation towards personalized nanomedicine, furthermore, key pivotal patient- and formulation-oriented challenges (e.g., patients' genomic/proteomic profiles and PK/PD properties) must be addressed before any clinical interventions. This review provides comprehensive insights into the smart GrNSs and discusses their applications for the concurrent diagnosis and treatment of solid tumors.

Graphene quantum dot modified glassy carbon electrode for the determination of doxorubicin hydrochloride in human plasma.

Low toxic graphene quantum dot (GQD) was synthesized by pyrolyzing citric acid in alkaline solution and characterized by ultraviolet--visible (UV-vis) spectroscopy, X-ray diffraction (XRD), atomic force microscopy (AFM), spectrofluorimetery and dynamic light scattering (DLS) techniques. GQD was used for electrode modification and electro-oxidation of doxorubicin (DOX) at low potential. A substantial decrease in the overvoltage (-0.56 V) of the DOX oxidation reaction (compared to ordinary electrodes) was observed using GQD as coating of glassy carbon electrode (GCE). Differential pulse voltammetry was used to evaluate the analytical performance of DOX in the presence of phosphate buffer solution (pH 4.0) and good limit of detection was obtained by the proposed sensor. Such ability of GQD to promote the DOX electron-transfer reaction suggests great promise for its application as an electrochemical sensor.

Graphene quantum dot modified glassy carbon electrode for the determination of doxorubicin hydrochloride in human plasma$ / 药物分析学报

Low toxic graphene quantum dot (GQD) was synthesized by pyrolyzing citric acid in alkaline solution and characterized by ultraviolet–visible (UV–vis) spectroscopy, X-ray diffraction (XRD), atomic force micro-scopy (AFM), spectrofluorimetery and dynamic light scattering (DLS) techniques. GQD was used for electrode modification and electro-oxidation of doxorubicin (DOX) at low potential. A substantial de-crease in the overvoltage ( ? 0.56 V) of the DOX oxidation reaction (compared to ordinary electrodes) was observed using GQD as coating of glassy carbon electrode (GCE). Differential pulse voltammetry was used to evaluate the analytical performance of DOX in the presence of phosphate buffer solution (pH 4.0) and good limit of detection was obtained by the proposed sensor. Such ability of GQD to promote the DOX electron-transfer reaction suggests great promise for its application as an electrochemical sensor.