DARU Journal of Pharmaceutical Sciences最新文献

{"title":"Smoking cessation pharmacotherapy; varenicline or bupropion?","authors":"Fatemeh Rahimi, Ali Massoudifar, Roya Rahimi","doi":"10.1007/s40199-024-00539-6","DOIUrl":"https://doi.org/10.1007/s40199-024-00539-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>Tobacco smoking is a worldwide health problem and one of the leading causes of premature deaths in last years. As there are lots of researches focusing on cessation strategies with attention to pharmacotherapy and behavioral counseling, the aim of this study was to compare two of the first-line FDA-approved pharmacotherapies for smoking cessation; varenicline and bupropion.</p><h3 data-test=\"abstract-sub-heading\">Evidence acqusition</h3><p>This writing is an overview of researches published in Pubmed database from 2012 to 2022 with “Varenicline” and “Bupropion” as key words. Among the researches that were found, 24 articles were selected which mainly focused on comparison of these two medicines.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Varenicline and bupropion are known as non-nicotinic pharmacotherapy and have been used in addition to nicotine replacement therapy for smoking cessation. Varenicline is partial agonist for α4β2 nicotinic acetyl choline receptors while bupropion, classified as an atypical antidepressant, is actually a norepinephrine and dopamine reuptake inhibitor. Although these treatments can result in some adverse effects including nausea, insomnia, anxiety, irritability, fatigue and abnormal dreams, their efficacy in reduction of craving and also maintenance of abstinence is well been studied and approved by FDA. Moreover, adverse effects are usually mild to moderate clinical symptoms which can be tolerated and also easily managed and prevented in cases.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The efficacy and tolerability of varenicline and bupropion as treatments for smoking cessation is well understood. However, studies have shown that varenicline seems to be more effective in maintaining of abstinence and also reducing craving than bupropion and NRT.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid management strategies for diabetic patients align with an evidence-based guideline.","authors":"Mona Kargar, Noushid Zare, Aarefeh Jafarzadeh Kohneloo, Fatemeh Afra, Elham Hadidi, Kheirollah Gholami","doi":"10.1007/s40199-024-00534-x","DOIUrl":"https://doi.org/10.1007/s40199-024-00534-x","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM) increases the risk of cardiovascular diseases (CVD) significantly. Statins are recommended for all diabetic patients aged ≥ 40 years to alleviate this risk.</p><p><strong>Objectives: </strong>This study aimed to determine the status of the implementation of the recommendations of lipid management strategies for diabetic patients.</p><p><strong>Methods: </strong>In this cross-sectional study, 500 patients with DM, aged ≥ 40 referring to a public pharmacy with at least one diabetic medication in their prescription, were enrolled. Patients' demographics, lipid panel data, medications, personal and family history of atherosclerotic cardiovascular disease (ASCVD), and risk factors for ASCVD were documented. The appropriateness of stain dosing intensity was judged based on the American Diabetes Association (ADA) guideline.</p><p><strong>Results: </strong>The mean ± SD of the age of patients was 61.39 ± 10.49 years. Among patients, 238 (47.6) were men. More than half of the patients were subject to receiving primary prevention (59.8%, n = 299). For 80.8% (n = 404) of patients, a statin, most frequently atorvastatin (61.8%), was prescribed. The appropriate statin dose based on the guideline for 470 patients (94%), was high-intensity statin. In 70.6% (n = 353) of patients, lipid management was not in accordance with the guideline. Patients with ASCVD were more likely to receive the statins and the appropriate doses compared to patients without ASCVD (p-value < 0.001).</p><p><strong>Conclusion: </strong>Despite a relatively high percentage of patients who received statins, the lipid management in most patients was not in accordance with the guideline. The profound problem was the suboptimal dosage of statins. Investigating the reasons and barriers of the appropriate management can be helpful. Additionally, since patients without ASCVD who should receive statins for primary prevention were significantly less likely to receive statins and evidence-based doses, more attention is needed for this population.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glatiramer acetate in situ forming gel, a new approach for multiple sclerosis treatment.","authors":"Anahita Shobeirean, Hossein Attar, Reyhaneh Varshochian, Mohammad Amin Rezvanfar","doi":"10.1007/s40199-024-00532-z","DOIUrl":"https://doi.org/10.1007/s40199-024-00532-z","url":null,"abstract":"<p><strong>Background: </strong>Glatiramer acetate (GA), a commonly used treatment for multiple sclerosis (MS), requires long-term frequent injections to ensure its effectiveness. This often leads to adverse effects, patient noncompliance, and economic inefficiency.</p><p><strong>Objectives: </strong>In this study, poloxamer, as a thermosensitive polymer modified by chitosan (CS) and hyaluronic acid (HA), was employed to prepare an in situ forming prolonged release formulation of GA to overcome the problems derived from frequent repeated injections and to enhance the patient compliance.</p><p><strong>Methods: </strong>The sol-gel formulation was produced through a cold method and optimized using design of experiments. The final product was characterized in terms of gelation time (GT), rheological behaviors, morphological properties, assay, and drug release kinetics.</p><p><strong>Results: </strong>The in vitro release rate of GA during the first 24 h was quite rapid, but then it continued at a slower rate of 0.05 mg ml^-1h^-1. The in vivo analysis after the subcutaneous injections showed lower levels of IL-5, IL-13, and uric acid (UA) in mice treated with the gel formulation compared with those receiving free GA in the first few days. However, after 10 days, significantly higher concentrations were detected, which continued to increase slowly.</p><p><strong>Conclusion: </strong>It can be concluded that the designed thermosensitive sol-gel formula is capable of extending the effectiveness of GA and can be considered as a promising sustained release formulation for the treatment of MS.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of the ethnomedicinal, phytochemical, and pharmacological properties of the Ferulago genus based on Structure-Activity Relationship (SAR) of coumarins.","authors":"Farid Dabaghian, Shokoufeh Aalinezhad, Alaleh Riazati Kesheh, Niloufar Azargashb, Ramin Ansari, Mohammad Reza Shams Ardekani, Seyed Ahmad Emami, Mahnaz Khanavi, Mohammad Reza Delnavazi","doi":"10.1007/s40199-024-00530-1","DOIUrl":"https://doi.org/10.1007/s40199-024-00530-1","url":null,"abstract":"<p><strong>Background: </strong>The Ferluago W.D.J. Koch genus includes 48 accepted perennial herbs that are distributed in the Mediterranean region, Southeast Europe, Central and Middle East of Asia. These plants are widely used in folk and conventional medicine due to their biological benefits such as anti-microbial, anti-inflammatory, anti-cancer, and immunomodulatory properties. Conducting a comprehensive review based on the structure activity relationships (SARs) of the coumarins, which has not been previously documented, can lead to a better insight into the genus Ferulago and its beneficial therapeutic activities.</p><p><strong>Methods: </strong>This review covers literature from 1969 to 2023, were collected from various scientific electronic databases to review phytochemical, pharmacological, and ethnopharmacological data of Ferulago species, as well as latest information on the SAR of reported coumarins from this genus.</p><p><strong>Results: </strong>Phytochemical studies showed that the biological actions of this genus are mediated by the reported specialized metabolites, such as coumarins and flavonoids. Simple coumarins, prenylated coumarins, furanocoumarins, and pyranocoumarins are the largest subclasses of coumarins found in diverse Ferulago species, which have discussed the biological effects of them with a focus on the Structure-Activity Relationship (SAR). For example, prenylated coumarins have shown potential leishmanicidal and anti-neuropsychiatric effects when substituted with a prenyl group at the 7-hydroxy, as well as the C₆ and C₈ positions in their scaffold. Similarly, furanocoumarins exhibit varied biological activities such as anti-inflammatory, anti-proliferative, and anti-convulsant effects. Modifying substitutions at the C₅ and C₆ positions in furanocoumarins can enhance these activities.</p><p><strong>Conclusion: </strong>This study conducted a comprehensive review of all available information on the phytochemical and pharmacological characteristics of Ferulago species. Given the high occurrence of coumarins in this genus, which exhibit potential anti-Alzheimer and anti-microbial properties, it presents promising new therapeutic avenues for addressing these common issues. Further investigation is needed to understand the molecular-level mechanisms of action and to explore their clinical applications.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics of Loxoprofen and its alcoholic metabolites in healthy Korean men.","authors":"Ji-Hun Jang, Ho-Suk Kang, Seung-Hyun Jeong","doi":"10.1007/s40199-024-00533-y","DOIUrl":"https://doi.org/10.1007/s40199-024-00533-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Loxoprofen has been actively used clinically to relieve musculoskeletal pain and inflammatory symptoms. However, there are few reports on quantitative pharmacokinetic (PK) prediction tools and diversity analyzes for loxoprofen within populations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The aim of this study was to identify effective covariates associated with explaining inter-individual PK variability through a population pharmacokinetic (Pop-PK) modeling approach for loxoprofen, and to provide a starting point for establishing scientific dosing regimens.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;The bioequivalence PK results of loxoprofen performed on 52 healthy Korean men and the physiological and biochemical parameters derived from each individual were used as base data for the development of a Pop-PK model of loxoprofen. In order to simultaneously predict the PKs of the active form according to loxoprofen exposure, previously reported PK results of trans-alcohol loxoprofen, an active metabolite of loxoprofen, were used to expand the model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The Pop-PK profiles of loxoprofen were described in terms of the basic structure of a non-sequential two absorption with 2-disposition compartment, and for inter-individual PK variations, peripheral compartment volume of distribution could be correlated with body surface area (BSA), and central compartment clearance with creatinine clearance (CrCL) and albumin levels. As a result of the model simulation, the concentrations of loxoprofen and its alcoholic metabolites in plasma significantly decreased as CrCL and albumin levels increased and decreased, respectively. On the other hand, it was confirmed that the higher the BSA, the greater the distribution of loxoprofen to the periphery, and the minimum concentrations of loxoprofen and alcoholic metabolites in plasma in steady-state increased by approximately 1.78-2 times, while the fluctuation between maximum and minimum concentrations decreased. The results suggest that patients with large BSA, impaired renal function, and high serum albumin levels may have significantly higher plasma exposure to loxoprofen and trans-alcohol loxoprofen. It was also suggested that the potential side effects in the gastrointestinal system and various tissues and the level of exposure in plasma due to long-term application of loxoprofen in this patient group could be causally explained.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study provides a very useful starting point for a scientific precision medicine approach to loxoprofen by discovering effective covariates and establishing a quantitative model that can explain the diversity of loxoprofen PKs within the population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinical trial registration: &lt;/strong&gt;The clinical study protocol used in this study was thoroughly reviewed and approved by the Institutional Review Board of the Institute of Bioequivalence and Bridging Study, Chonnam National University, Gwangju, Rep","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dispersive micro-solid phase extraction based on two MOFs as highly effective adsorbents for analysis of nilotinib in plasma and wastewater.","authors":"Azra Takhvar, Somaye Akbari, Effat Souri, Reza Ahmadkhaniha, Ali Morsali, Mohammad Reza Khoshayand, Mohsen Amini, Alireza Taheri","doi":"10.1007/s40199-024-00531-0","DOIUrl":"https://doi.org/10.1007/s40199-024-00531-0","url":null,"abstract":"<p><strong>Background: </strong>Nilotinib (NIL) is a prescription medication employed in the treatment of specific types of leukemia, namely chronic myelogenous leukemia (CML). The determination of NIL levels in patients undergoing treatment for CML is of paramount importance for effective management of treatment and toxicity. Also, monitoring and controlling its level in wastewater sources could help scientists to identify potential hotspots of contamination and take appropriate measures to mitigate their impact on the environment and public health.</p><p><strong>Objectives: </strong>This study presents a D-µ-SPE technique utilizing two MOFs as adsorbents for the efficient detection of nilotinib in plasma and wastewater samples for the first time.</p><p><strong>Methods: </strong>Two highly effective MOFs, MIL-101(Fe) and MIL-53(Al), were synthesized and applied as dispersive micro-solid phase extraction (D-µ-SPE) adsorbents for the extraction of nilotinib coupled with HPLC-UV in a short time of analysis. Experimental parameters affecting extraction efficacy such as adsorbent amount, ionic strength, pH value, adsorption-desorption time and type of elution solvent, were optimized.</p><p><strong>Results: </strong>Under optimal experimental conditions, the linear dynamic was achieved in the range of 0.25-5.00 µg/mL in human plasma and 0.01-0.20 µg/mL in wastewater. The extraction recovery was in the range of 89.18-91.53% and 94.39-99.60% for nilotinib and MIL-101(Fe) and also 91.22-97.35% and 98.14-100.78% for nilotinib and MIL-53(Al) from human plasma and wastewater respectively.</p><p><strong>Conclusion: </strong>HPLC-UV determination of nilotinib after the D-µ-SPE method showed acceptable accuracy and precision in both plasma and wastewater. In comparison between the two adsorbents, the extraction procedure was easier and faster with MIL-53(Al) as the adsorbent.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid derivatives containing dimethyl fumarate and benzothiazole scaffolds for the potential treatment of multiple sclerosis; in silico & in vivo study.","authors":"Seyedeh Azin Mirmotahari, Mehdi Aliomrani, Farshid Hassanzadeh, Hajar Sirous, Mahboubeh Rostami","doi":"10.1007/s40199-024-00529-8","DOIUrl":"https://doi.org/10.1007/s40199-024-00529-8","url":null,"abstract":"<p><strong>Background: </strong>Multiple Sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the CNS. Riluzole and dimethyl fumarate (DMF) are two FDA-approved drugs to treat amyotrophic lateral sclerosis (ALS) and MS. Riluzole (a benzothiazole derivative) inhibits glutamate release from nerve terminals by antagonizing the N-Methyl-D-Aspartate (NMDA) receptor, and DMF upregulates anti-oxidative pathways.</p><p><strong>Objectives: </strong>Herein, using molecular hybridization strategy, we synthesized some new hybrid structures of Riluzole and DMF through some common successive synthetic pathways for evaluating their potential activity for remyelination in MS treatment.</p><p><strong>Methods: </strong>Molecular docking experiments assessed the binding affinity of proposed structures to the NMDA active site. The designed structures were synthesized and purified based on well-known chemical synthesis procedures. Afterward, in vivo evaluation for their activity was done in the C57Bl/6 Cuprizone-induced demyelination MS model.</p><p><strong>Results and conclusion: </strong>The proposed derivatives were recognized to be potent enough based on docking studies (ΔG_bind of all derivatives were -7.2 to -7.52 compare to the Ifenprodil (-6.98) and Riluzole (-4.42)). The correct structures of desired derivatives were confirmed using spectroscopic methods. Based on in vivo studies, D4 and D6 derivatives exhibited the best pharmacological results, although only D6 showed a statistically significant difference compared to the control. Also, for D4 and D6 derivatives, myelin staining confirmed reduced degeneration in the corpus callosum. Consequently, D4 and D6 derivatives are promising candidates for developing new NMDA antagonists with therapeutic value against MS disorders.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plausible mechanism of drug resistance and side-effects of COVID-19 therapeutics: a bottleneck for its eradication.","authors":"Swarnali Das, Sreyashi Nath, Shahjahan, Sanjay Kumar Dey","doi":"10.1007/s40199-024-00524-z","DOIUrl":"https://doi.org/10.1007/s40199-024-00524-z","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 pandemic has turned our world upside down by meddling with our normal lives. While there is no definitive drug against SARS-CoV-2, antiviral drugs that are already in the market, are being repurposed against it, could now complete long-term as well as all age-specific investigations, and they are successful in saving millions of lives. Nevertheless, side-effects are emergingly seen in the patients undergoing treatment, and ineffectiveness is increasingly found due to the emerging notorious variants of the virus. Many of them are also facing serious co-infections including black fungus, Zika, and H1N1 virus to name a few.</p><p><strong>Objectives: </strong>Therefore, this review highlights both drug resistance, their side-effects, and the significance for proper and long-term clinical trials of all age groups including children.</p><p><strong>Methods: </strong>We have explored and proposed the mechanisms of drug resistance that may arise due to the misuse or overuse of drugs based on available experimental reports.</p><p><strong>Results: </strong>The review provides solutions to the aforesaid issues of drug-resistance and side-effects by providing combination therapies, ancillary treatments, and other preventive strategies that can be useful in preventing drawbacks thereby curbing COVID-19 or similar future infections to maintain our normal lives.</p><p><strong>Conclusion: </strong>COVID-19 and its long-term effects, if any, can be eradicated with strategic and mindful use of related therapeutics in a controlled manner.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicological effect of acetaminophen, metamizole, and nimesulide cocktail on early development of zebrafish.","authors":"Wellington Fernandes de Carvalho, Ednalva de Souza Pereira Lima, Whocely Victor de Castro, Ralph Gruppi Thomé, Hélio Batista Santos","doi":"10.1007/s40199-024-00528-9","DOIUrl":"https://doi.org/10.1007/s40199-024-00528-9","url":null,"abstract":"<p><strong>Background: </strong>Several countries' most incorrectly discarded medicines are acetaminophen (ACM), metamizole (MTZ), and nimesulide (NMS). These xenobiotics easily reach the aquatic environment; such contamination is very important for the health of humans and other species, yet little explored.</p><p><strong>Objectives: </strong>To evaluate the cocktail effect of ACM, MTZ, and NMS during zebrafish's initial development.</p><p><strong>Methods: </strong>Zebrafish embryos 6-8 h post-fertilization (hpf) were exposed to different concentrations of ACM, MTZ, and NMS, separately, to obtain the 50% lethal concentrations (LC₅₀). Next, the embryos were exposed to distinct concentrations of the cocktail (LC₅₀/2, LC₅₀/5, LC₅₀/10, and LC₅₀/20) in a semi-static system. Samples were analyzed 0, 24, 48, and 96 h after exposure, and the drugs' concentrations in E3 medium were assessed by high-performance liquid chromatography. For embryotoxicity evaluation, the mortality, hatching, and heart rates; total length; and pericardial and yolk sac areas were determined. In addition, body malformations, edemas, presence of pigmentation, and histopathological assessments were also recorded.</p><p><strong>Results: </strong>The LC₅₀ values obtained for MTZ, ACM, and NMS were 4.69 mgmL^-1, 799.98 μgmL^-1, and 0.92 μgmL^-1, respectively. No difference was observed between the drugs' nominal and observed concentrations at each time point. The cocktail significantly induced mortality and decreased hatching in the LC₅₀/10, LC₅₀/5, and LC₅₀/2 groups. Additionally, body malformations, pigmentation loss, and yolk sac and pericardial edemas were observed in the cocktail groups. The cocktail groups' larvae had decreased total length and slower heart rates compared to the controls (p < 0.05). The histopathological assessment showed that yolk sac edema promoted severe histological changes in the esophageal-intestine junction and intestine in larvae treated with cocktails. Moreover, PAS-positive structures decreased in the esophageal-intestine junction, intestine, and liver in larvae exposed to pharmaceutical cocktails.</p><p><strong>Conclusion: </strong>This study's findings suggest the cocktail of ACM, MTZ, and NMS may be hazardous to aquatic organisms in case of environmental contamination.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation of poly(vinyl alcohol) nanofibers containing disulfiram-copper complex by electrospinning: a potential delivery system against melanoma.","authors":"Gomaa F El Fawal, Marwa M Abu-Serie","doi":"10.1007/s40199-024-00527-w","DOIUrl":"https://doi.org/10.1007/s40199-024-00527-w","url":null,"abstract":"<p><strong>Background: </strong>Melanoma poses a significant threat to human health, making the development of a safe and effective treatment a crucial challenge. Disulfiram (DS) is a proven anticancer drug that has shown effectiveness when used in combination with copper (DS-Cu complex).</p><p><strong>Objectives: </strong>This study focuses on encapsulation of DS-copper complex into nanofiber scaffold from polyvinyl alcohol (PVA) (DS-Cu@PVA). In order to increase bioavailability towards melanoma cell lines and decrease its toxicity.</p><p><strong>Methods: </strong>The scaffold was fabricated through an electrospinning process using an aqueous solution, and subsequently analyzed using ART-Fourier transform infrared spectroscopy (ART-FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX). Additionally, cellular cytotoxicity, flow cytometry analysis, and determination of caspase 3 activity were conducted to further characterize the scaffold.</p><p><strong>Results: </strong>The results confirmed that encapsulation of DS-Cu complex into PVA was successful via different characterization. The scanning electron microscopy (SEM) analysis revealed that the diameter of the nanofibers remained consistent despite the addition of DS-Cu. Additionally, ATR-FTIR confirmed that the incorporation of DS-Cu into PVA did not significantly alter the characteristic peaks of PVA. Furthermore, the cytotoxicity assessment of the DS-Cu@PVA nanofibrous scaffold using human normal skin cells (HFB4) demonstrated its superior biocompatibility compared to DS-Cu-free counterparts. Notably, the presence of DS-Cu maintained its effectiveness in promoting apoptosis by increasing cellular reactive oxygen species, proapoptotic gene expression, and caspase 3 activity, while simultaneously reducing glutathione levels and oncogene expression in human and mouse melanoma cell lines (A375 and B16F10, respectively). Overall, these findings suggest that the addition of DS-Cu to PVA nanofibers enhances their biocompatibility and cytotoxic effects on melanoma cells, making them a promising candidate for biomedical applications.</p><p><strong>Conclusion: </strong>The findings indicate that the targeted delivery of DS-Cu onto a PVA nanofiber scaffold holds potential approach to enhance the efficacy of DS-Cu in combating melanoma.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}