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Evaluation of the consumption pattern and efficacy of Linezolid in COVID-19 hospitalized patients in a hospital in Tehran-Iran. 伊朗德黑兰某医院新冠肺炎住院患者利奈唑胺消费模式及疗效评价
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-03 DOI: 10.1007/s40199-024-00554-7
Alireza Tavasoli Rostami, Morteza Izadi, Mohsen Saberi, Mehdi Raei, Mostafa Soodmand, Khadijeh Nasiri, Hossein Mardani Nafchi, Mahdi Bagheri

Background: The inappropriate use of antibiotics increases the costs of treatment, antibiotic resistance, increased disease length and duration of hospital stay.

Objectives: The aim of this study was investigating the pattern of use and effectiveness of the Linezolid in COVID-19 hospitalized patients.

Methods: In this retrospective cross-sectional analytical study was carried out from February 2020 (from the beginning of the pandemic in Iran) to the end of September 2020, 32 COVID-19 patients that used Linezolid were included. The data retrieved from medical document's unit and analysis was performed by SPSS statistical software version 20.

Results: According to the three elements of the 1- culture of resistant bacteria 2-the correct daily dose and 3-adequate duration of the drug, consumption pattern of Linezolid was irrational in 24 (75%) COVID-19 patients and it was rational only in 8 (25%) patients. Twenty-three (71.9%) patients received sufficient doses of the drug and 9 (28.1%) patients did not receive the required minimum dose. Four (50%) patients who rationally received Linezolid improved and the remaining 4 died. Leukopenia occurred in 1 patient (3.1%), anemia appeared in 24 individuals (75%), and 15 patients (46.9%) developed thrombocytopenia.

Conclusion: We suggest that the prescription of Linezolid is in accordance with the standard instructions and the stewardship antibiotic program to reduce the medication costs, drug side effects, and the prevalence of antibiotic resistance.

背景:抗生素的不当使用增加了治疗费用,抗生素耐药性,增加了疾病的长度和住院时间。目的:探讨利奈唑胺在COVID-19住院患者中的使用模式和疗效。方法:本回顾性横断面分析研究于2020年2月(从伊朗大流行开始)至2020年9月底,纳入32例使用利奈唑胺的COVID-19患者。数据从医学文献单元中检索,采用SPSS统计软件20版进行分析。结果:根据耐药菌培养2-正确日剂量3-用药时间3个要素,24例(75%)COVID-19患者利奈唑胺的用药模式不合理,仅8例(25%)患者用药模式合理。23例(71.9%)患者接受了足够剂量的药物治疗,9例(28.1%)患者未接受所需的最低剂量治疗。合理使用利奈唑胺的患者4例(50%)病情好转,其余4例死亡。白细胞减少1例(3.1%),贫血24例(75%),血小板减少15例(46.9%)。结论:利奈唑胺的处方应符合标准说明书和抗生素管理程序,以降低用药成本、药物副作用和抗生素耐药率。
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引用次数: 0
The effect of biosynthesized zinc oxide nanoparticles on gene expression and apoptosis in triple-negative breast cancer cells. 生物合成氧化锌纳米颗粒对三阴性乳腺癌细胞基因表达和凋亡的影响。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-28 DOI: 10.1007/s40199-024-00553-8
Hannaneh Zarrinnahad, S Ahmad Dehdast, Ghazaleh Chizari Fard, Mitra Nourbakhsh, Mohammad Kazem Koohi, Ghodratollah Panahi, Amin Karimpour, S Mehdi Rezayat, Mohammad Shabani

Objective(s): Some forms of breast cancer such as triple-negative phenotype, are serious challenge because of high metastatic cases, high mortality and resistance to conventional therapy motivated the search for alternative treatment approaches. Nanomaterials are promising candidates and suitable alternatives for improving tumor and cancer cell treatments.

Materials and methods: Biosynthesis of ZnO NPs by help of Berberis integerrima fruit extract, has been done. Analysis of Zinc Oxide NPs using DLS, FTIR, SEM, and EDS techniques have been performed. Moreover, biological activities of ZnO NPs evaluated through MTT method, Flow cytometry, and real time PCR methods. Biocatalytic and apoptotic activity of ZnO NPs on healthy HFF (human fibroblast cell line), MDA-MB 231, and MDA-MB 468 (triple negative breast cancer cell lines, (TNBC)) evaluated. Furthermore, Bax, Bcl-2 and caspase-3 apoptotic genes expression changes in cancer cells assessed in compare to GAPDH as a house keeping gene.

Results: Physico-chemical investigation demonstrated ZnO NPs were confirmed by Berberis integerrima fruit extract for the first time. The MTT assay and Flow cytometry results indicated biocompatibility of the ZnO NPs in normal cell line and high anticancer potential against TNBC MDA-MB-231 and MDA-MB-468 cell lines. The IC50 of ZnO NPs were 104.4 and 44.86, 20.96 after 24 hours for HFF, MDA-MB-231 and MDA-MB-468 cells, respectively.

Conclusion: The current research showed a fast, cost effective and ecofriendly method for ZnO NPs nanoparticle synthesis. Furthermore, In vitro data analysis demonstrated biocompatibility and highly anticancer effects of biosynthesized ZnO NPs against TNBC cancerous cells.

目的:某些类型的乳腺癌,如三阴性表型,是严重的挑战,因为高转移病例,高死亡率和对传统治疗的耐药性促使寻找替代治疗方法。纳米材料是改善肿瘤和癌细胞治疗的有希望的候选者和合适的替代品。材料与方法:以小檗果实提取物为原料,进行了氧化锌纳米粒子的生物合成。使用DLS, FTIR, SEM和EDS技术对氧化锌NPs进行了分析。此外,通过MTT法、流式细胞术和实时PCR法对氧化锌NPs的生物活性进行了评价。氧化锌NPs对健康HFF(人成纤维细胞系)、MDA-MB 231和MDA-MB 468(三阴性乳腺癌细胞系,TNBC)的生物催化和凋亡活性进行了评价。此外,与作为管家基因的GAPDH相比,评估了Bax、Bcl-2和caspase-3凋亡基因在癌细胞中的表达变化。结果:小檗果实提取物首次在理化性质上证实了氧化锌NPs的存在。MTT实验和流式细胞术结果表明ZnO NPs在正常细胞系中具有良好的生物相容性,对TNBC MDA-MB-231和MDA-MB-468细胞系具有较高的抗癌潜力。HFF、MDA-MB-231和MDA-MB-468细胞24 h后ZnO NPs的IC50分别为104.4和44.86、20.96。结论:本研究为ZnO纳米粒子的合成提供了一种快速、经济、环保的方法。此外,体外数据分析表明,生物合成的ZnO NPs对TNBC癌细胞具有生物相容性和高度的抗癌作用。
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引用次数: 0
In-vivo and in-vitro assessment of curcumin loaded bile salt stabilized nanovesicles for oral delivery. 口服姜黄素胆盐稳定纳米囊的体内和体外评估。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-23 DOI: 10.1007/s40199-024-00544-9
Fahima M Hashem, Dalia Elkhateeb, Marwa M Ali, Rania S Abdel-Rashid

Background: Bile salts enriched nanovesicles (bilosomes) have been attention worthy in the past few years due to their distinctive effect on the enhancement of drug delivery through various physiological administration routes. Oral delivery of multifunctioning phytochemical curcumin has faced a lot of difficulties due to its scarce solubility and poor oral bioavailability.

Objective: The current investigation aimed to develop curcumin loaded bilosomes for improvement of oral curcumin bioavailability with maximum efficiency and safety.

Methods: The effect of formulation variables (type of span, SDC % to total lipid content Span/Cholesterol molar ratio) on physicochemical characterization and in vitro drug release in simulated intestinal fluid was investigated. Furthermore, in-vivo protective effect of bilosomes on hepatic and renal functions was also studied.

Results: and conclusion. The results revealed that the best curcumin loaded bilosomal formulation showed spherical nanovesicular morphology with particle size 145.1 ± 19.42 nm with highly reasonable %EE (93%), Zeta potential (≥ -30mv), prominent controlled in-vitro release reaching 55.18 ± 1.10 after 96 h. The formulation also showed good storage stability with negligible differences in physical features and content. The IC50 values of bilosomal, niosomal, and free curcumin were 216.50, 211.44, and 121.63 mmol/ml, respectively revealing that the unencapsulated curcumin displayed high toxicity on Caco2 cell line (nearly 2 folds). Additionally, the prepared bilosomes showed significant in-vivo hepatic and renal protection in liver cirrhosis induced rats with conservation to all liver and renal markers and histopathological morphology. The study assumes the effectiveness and safety of oral delivery of curcumin loaded bile salts stabilized nanovesicles and its powerful commandment for further investigations.

背景:胆盐富集纳米囊泡(胆囊体)由于其通过各种生理给药途径增强药物传递的独特作用,在过去的几年里受到了人们的关注。多功能植物化学物质姜黄素由于其溶解度低、口服生物利用度差,口服给药面临许多困难。目的:开发姜黄素载体,最大限度地提高口服姜黄素的生物利用度。方法:考察制剂类型、SDC % /总脂质/胆固醇摩尔比对制剂理化性质和体外模拟肠液药物释放的影响。此外,还研究了胆小体在体内对肝肾功能的保护作用。结果:及结论。结果表明,最佳的姜黄素载体颗粒剂为球形纳米泡状,粒径为145.1±19.42 nm, EE %(93%)合理,Zeta电位≥-30mv, 96 h体外控释量达到55.18±1.10,具有良好的储存稳定性,物理特征和含量差异可忽略。胆囊体、膜体和游离姜黄素的IC50值分别为216.50、211.44和121.63 mmol/ml,表明未包封的姜黄素对Caco2细胞株具有近2倍的高毒性。此外,制备的胆囊体在肝硬化大鼠体内表现出明显的肝脏和肾脏保护作用,对所有肝脏和肾脏标志物和组织病理形态都有保护作用。本研究假设了口服姜黄素胆盐稳定纳米囊的有效性和安全性,并为进一步的研究提供了强有力的指导。
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引用次数: 0
High-performance liquid chromatography method for measuring Captopril: an empirical study on hydrogel film permeability test. 测量卡托普利的高效液相色谱法:水凝胶薄膜渗透性试验的经验研究。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-20 DOI: 10.1007/s40199-024-00552-9
Siti Fatriyah, Noverra Mardhatillah Nizardo, Delly Ramadon

Background: High-performance liquid chromatography (HPLC) has emerged as a highly sensitive and versatile analytical technique for quantifying antihypertensive drugs, such as Captopril (CAP). This study focused on the optimization and validation of an HPLC method for quantifying CAP in an in vitro hydrogel permeability test.

Objectives: The main objective of this study was to develop and validate an HPLC method for quantifying CAP in an in vitro hydrogel permeability test.

Methods: The HPLC method employed a C18 column (Waters, Sunfire, 5 μm; 250 × 4.6 mm) and a mobile phase consisting of methanol-water (85% v/v orthophosphoric acid) in a 55:45 (v/v) ratio at a flow rate of 0.5 mL/min. The UV-Vis detector was configured to detect CAP at a wavelength of 220 nm. The hydrogel film used in the permeability test was prepared using poly (vinyl alcohol)/poly (vinyl caprolactam) (PVA/PNVCL) with citric acid as a crosslinking agent.

Results: All results met the validation parameters according to ICH Guideline. The HPLC method showed consistent retention time (4.7-4.9 min), linearity (1-50 µg/mL; r = 0.9995), accuracy (98.11-101.78%), precision (RSD ≤ 2%), and LoD/LoQ (0.19/0.62 µg/mL). The developed HPLC method was successfully applied to an in vitro permeability test using horizontal diffusion cells. The results demonstrated that CAP permeated through the swollen hydrogel film, with a cumulative drug permeation exceeding 30%.

Conclusion: This highlighted the method's utility in assessing drug transport properties through hydrogels. The validated HPLC method demonstrates robustness and reliability for quantifying CAP in the hydrogel permeability test.

背景:高效液相色谱法(HPLC)作为一种高灵敏度和多用途的分析技术被用于定量检测抗高血压药物,如卡托普利(CAP)。本研究主要对体外水凝胶渗透性试验中CAP的HPLC定量方法进行优化和验证。目的:本研究的主要目的是建立并验证体外水凝胶渗透性试验中CAP的高效液相色谱定量方法。方法:采用高效液相色谱法,色谱柱为C18 (Waters, Sunfire, 5 μm;250 × 4.6 mm),流动相为甲醇-水(85% v/v正磷酸),比为55:45 (v/v),流速为0.5 mL/min。紫外可见检测器的检测波长为220 nm。采用柠檬酸为交联剂,以聚乙烯醇/聚乙烯醇己内酰胺(PVA/PNVCL)为原料制备透水性试验用水凝胶膜。结果:所有结果均符合ICH指南的验证参数。高效液相色谱法显示保留时间一致(4.7 ~ 4.9 min),线性(1 ~ 50µg/mL);r = 0.9995),精度(98.11 - -101.78%),精密(相对标准偏差≤2%)、定量限和LoD /(0.19/0.62µg / mL)。所建立的高效液相色谱法成功地应用于水平扩散细胞的体外通透性测定。结果表明,CAP通过肿胀的水凝胶膜渗透,累积药物渗透率超过30%。结论:该方法可用于评价药物在水凝胶中的转运特性。经验证的高效液相色谱法在水凝胶渗透性测试中定量CAP具有稳健性和可靠性。
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引用次数: 0
Electroceuticals: Unlocking the promise of therapies. 电子药品:释放治疗的希望。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-19 DOI: 10.1007/s40199-024-00549-4
Isha Mishra, Kajal Chaudhary, Vikram Sharma, Gaurav Krishna, Raghav Mishra

Objectives: Electroceuticals refers to the constantly growing disciplines of bioelectric and bioelectronic medication. These include a broad variety of devices that have been invented and are now being utilized in medical implants, wearable medical electronics, and bioelectronics. The primary aim of this study is to encompass several facets of electroceuticals, their applications, and recent advancements in the field of medical challenges.

Evidence acquisitions: A complete literature study was conducted, which included a comprehensive review of globally recognized scientific research databases.

Results: The progressive refinement and diminution of technology, in conjunction with swift advancements in comprehending the role of electrical pathways in the human body, have rendered it progressively viable to manipulate these pathways for therapeutic purposes.

Discussion and conclusion: Electrical stimulation impacts and modifies biological functioning and pathological processes in the body. In the contemporary era of medicine, health care practitioners from a variety of fields utilize electricity to cure disease or injury or to assess and diagnose using a variety of electrically driven medical tools.

目的:电子医学是指不断发展的生物电学和生物电子医学学科。这些包括已经发明的各种各样的设备,现在正在用于医疗植入物,可穿戴医疗电子产品和生物电子产品。本研究的主要目的是涵盖电子产品的几个方面,它们的应用,以及在医疗挑战领域的最新进展。证据获取:进行了一项完整的文献研究,其中包括对全球公认的科学研究数据库的全面审查。结果:技术的不断完善和减少,以及对人体电通路作用的理解的迅速进步,使得为治疗目的操纵这些通路逐渐可行。讨论和结论:电刺激影响和改变体内的生物功能和病理过程。在当代医学时代,来自各个领域的卫生保健从业者利用电来治疗疾病或损伤,或使用各种电动医疗工具进行评估和诊断。
{"title":"Electroceuticals: Unlocking the promise of therapies.","authors":"Isha Mishra, Kajal Chaudhary, Vikram Sharma, Gaurav Krishna, Raghav Mishra","doi":"10.1007/s40199-024-00549-4","DOIUrl":"10.1007/s40199-024-00549-4","url":null,"abstract":"<p><strong>Objectives: </strong>Electroceuticals refers to the constantly growing disciplines of bioelectric and bioelectronic medication. These include a broad variety of devices that have been invented and are now being utilized in medical implants, wearable medical electronics, and bioelectronics. The primary aim of this study is to encompass several facets of electroceuticals, their applications, and recent advancements in the field of medical challenges.</p><p><strong>Evidence acquisitions: </strong>A complete literature study was conducted, which included a comprehensive review of globally recognized scientific research databases.</p><p><strong>Results: </strong>The progressive refinement and diminution of technology, in conjunction with swift advancements in comprehending the role of electrical pathways in the human body, have rendered it progressively viable to manipulate these pathways for therapeutic purposes.</p><p><strong>Discussion and conclusion: </strong>Electrical stimulation impacts and modifies biological functioning and pathological processes in the body. In the contemporary era of medicine, health care practitioners from a variety of fields utilize electricity to cure disease or injury or to assess and diagnose using a variety of electrically driven medical tools.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 1","pages":"7"},"PeriodicalIF":2.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Trends analysis and future study of the pharmaceutical industry field: a scoping review. 医药工业领域的趋势分析与未来研究:范围综述。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-17 DOI: 10.1007/s40199-024-00550-x
Manuchehr Bashirynejad, Fatemeh Soleymani, Shekoufeh Nikfar, Abbas Kebriaeezadeh, Reza Majdzadeh, Behzad Fatemi, Ali Zackery, Nafiseh Zare

Objective: The main aim of this study was to explore and understand the emerging developments, changes, and patterns shaping the future of the pharmaceutical industry. The pharmaceutical industry is evolving rapidly due to scientific breakthroughs, societal changes, and technological advancements. Companies can adapt, and innovate to stay competitive and advance healthcare objectives by understanding the changes and patterns shaping the future.

Methods: We conducted a thorough Scoping Review across PubMed, Embase, Web of Science, and Scopus, focusing on future trends in the pharmaceutical industry. Studies were carefully selected based on predefined criteria, ensuring a comprehensive and relevant collection.

Results: We identified and selected 24 studies that met our predefined criteria from a pool of 3617 studies. These studies served as the foundation for a detailed exploration of trends within the pharmaceutical industry. This compilation offers a profound understanding of the diverse forces propelling change, including technological advancements, regulatory shifts, evolving market dynamics, and regional nuances.

Conclusions: This research highlights transformative trends such as artificial intelligence, 3D printing, blockchain technology, and digital integration revolutionizing drug discovery, development, manufacturing, and delivery. However, successful implementation hinges on addressing challenges through practical strategies, interdisciplinary collaborations, and region-specific considerations. Future research should explore implementation approaches, facilitating the effective translation of these innovations into tangible healthcare benefits. This forward-looking analysis empowers the pharmaceutical industry to strategically position itself for long-term success in addressing evolving global needs.

目的:本研究的主要目的是探索和了解塑造未来制药行业的新兴发展、变化和模式。由于科学突破、社会变革和技术进步,制药行业正在迅速发展。企业可以通过了解塑造未来的变化和模式来适应和创新,以保持竞争力并推进医疗保健目标。方法:我们对PubMed、Embase、Web of Science和Scopus进行了全面的Scoping综述,重点关注制药行业的未来趋势。研究是根据预先确定的标准精心挑选的,以确保全面和相关的收集。结果:我们从3617项研究中确定并选择了24项符合我们预定义标准的研究。这些研究为详细探讨制药工业的发展趋势奠定了基础。这份汇编提供了对推动变革的各种力量的深刻理解,包括技术进步、监管转变、不断变化的市场动态和区域细微差别。结论:这项研究突出了人工智能、3D打印、区块链技术和数字集成等变革趋势,这些趋势彻底改变了药物发现、开发、制造和交付。然而,成功的实施取决于通过切实可行的战略、跨学科合作和区域具体考虑来应对挑战。未来的研究应该探索实施方法,促进这些创新有效转化为有形的医疗保健效益。这种前瞻性分析使制药业能够在应对不断变化的全球需求方面取得长期成功的战略定位。
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引用次数: 0
Development of amphotericin B inclusion complex formulation in dissolvable microarray patches for intravaginal delivery. 两性霉素B包合物可溶微阵列贴片阴道内给药配方的研制。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-12 DOI: 10.1007/s40199-024-00546-7
Habiburrahim Burhanuddin, Cindy Kristina Enggi, Frederika Tangdilintin, Rizki Rachmad Saputra, Purnawan Pontana Putra, Sartini Sartini, Aliyah Aliyah, Rina Agustina, Juan Domínguez-Robless, Muhammad Aswad, Andi Dian Permana

Background: Amphotericin B (AMB) is a drug used to treat vulvovaginal candidiasis (VVC), which is a fungal infection affecting the vagina and vulva. Nevertheless, the substance's limited capacity to dissolve in water leads to poor absorption when taken orally, hence diminishing its therapeutic efficacy. In order to address this limitation, β-cyclodextrin (βCD) was used to create AMB in the form of an inclusion complex.

Objective: This study aims to enhance the solubility and bioavailability of AMB by formulating it into an inclusion complex with βCD. Subsequently, we developed dissolvable microarray patches (DMP) as a novel drug delivery system, optimizing the formulation for improved retention, penetration, and controlled release of AMB.

Methods: The stability of the AMB-βCD inclusion complx (IC) structure has been confirmed by employing molecular docking studies. The formulation of DMP involved the incorporation of IC with polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). The mechanical strength, ability to be inserted, and propensity to irritate Amphotericin B-Inclusion Complex-Dissolvable Microarray Patches (IC-DMP) were evaluated by laboratory experiments utilizing the porcine vaginal mucosal layer. Further investigations, such as Differential Scanning Calorimetry (DSC), were performed to assess the physicochemical characteristics of the IC.

Results: The solubility of the pure medication was greatly enhanced up to fourfold by the inclusion complex. The assessment of IC-DMP exhibited exceptional mechanical robustness and insertion abilities, with no indications of discomfort. Among the formulas tested in ex vivo vaginal kinetic experiments, Formula F3 had the most effective retention in the porcine vaginal mucosal layer. It had an AUC value of 208.02 ± 0.33 h.µg/cm3 and the highest Cmax value of 20.05 ± 0.06 µg/cm3. Therefore, Formula F3 was the most efficient formula in terms of vaginal drug delivery.

Conclusion: The integration of IC into the DMP system significantly enhances the solubility and bioavailability of AMB, facilitating its absorption in the circulatory system when applied intravaginally for vulvovaginal candidiasis treatment. These promising initial findings support further clinical evaluation of this novel drug delivery system.

背景:两性霉素B (AMB)是一种用于治疗外阴阴道念珠菌病(VVC)的药物,VVC是一种影响阴道和外阴的真菌感染。然而,该物质溶于水的能力有限,导致口服时吸收不良,从而降低了其治疗效果。为了解决这一限制,我们利用β-环糊精(βCD)以包合物的形式制备了AMB。目的:通过与βCD形成包合物,提高AMB的溶解度和生物利用度。随后,我们开发了可溶解微阵列贴片(DMP)作为一种新的药物递送系统,优化了配方,以提高AMB的保留、渗透和控释。方法:通过分子对接研究,证实了AMB-β - cd包合物(IC)结构的稳定性。DMP的配方是将IC与聚乙烯醇(PVA)和聚乙烯吡咯烷酮(PVP)掺入。利用猪阴道粘膜层进行实验室实验,评估两性霉素b包合物可溶微阵列贴片(IC-DMP)的机械强度、插入能力和刺激倾向。进一步的研究,如差示扫描量热法(DSC),评估了ic的物理化学特性。结果:包合物使纯药物的溶解度大大提高,可达四倍。评估显示IC-DMP具有出色的机械稳健性和插入能力,无不适迹象。在离体阴道动力学试验中,配方F3在猪阴道粘膜层的滞留效果最好。AUC值为208.02±0.33 h.µg/cm3,最大Cmax值为20.05±0.06µg/cm3。因此,在阴道给药方面,F3是最有效的配方。结论:将IC整合到DMP系统中,可显著提高AMB的溶解度和生物利用度,促进其在阴道内治疗外阴阴道念珠菌病时在循环系统中的吸收。这些有希望的初步发现支持对这种新型给药系统进行进一步的临床评估。
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引用次数: 0
Cellular and molecular aspects of drug resistance in cancers. 癌症耐药的细胞和分子方面。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-09 DOI: 10.1007/s40199-024-00545-8
Rahaman Shaik, M Shaheer Malik, Sreevani Basavaraju, Jihan Qurban, Fatimah M M Al-Subhi, Sathvika Badampudi, Jagruthi Peddapaka, Azeeza Shaik, Ahmad Abd-El-Aziz, Ziad Moussa, Saleh A Ahmed

Objectives: Cancer drug resistance is a multifaceted phenomenon. The present review article aims to comprehensively analyze the cellular and molecular aspects of drug resistance in cancer and the strategies employed to overcome it.

Evidence acquisition: A systematic search of relevant literature was conducted using electronic databases such as PubMed, Scopus, and Web of Science using appropriate key words. Original research articles and secondary literature were taken into consideration in reviewing the development in the field.

Results and conclusions: Cancer drug resistance is a pervasive challenge that causes many treatments to fail therapeutically. Despite notable advances in cancer treatment, resistance to traditional chemotherapeutic agents and novel targeted medications remains a formidable hurdle in cancer therapy leading to cancer relapse and mortality. Indeed, a majority of patients with metastatic cancer experience are compromised on treatment efficacy because of drug resistance. The multifaceted nature of drug resistance encompasses various factors, such as tumor heterogeneity, growth kinetics, immune system, microenvironment, physical barriers, and the emergence of undruggable cancer drivers. Additionally, alterations in drug influx/efflux transporters, DNA repair mechanisms, and apoptotic pathways further contribute to resistance, which may manifest as either innate or acquired traits, occurring prior to or following therapeutic intervention. Several strategies such as combination therapy, targeted therapy, development of P-gp inhibitors, PROTACs and epigenetic modulators are developed to overcome cancer drug resistance. The management of drug resistance is compounded by the patient and tumor heterogeneity coupled with cancer's ability to evade treatment. Gaining further insight into the mechanisms underlying medication resistance is imperative for the development of effective therapeutic interventions and improved patient outcomes.

目的:肿瘤耐药是一个多方面的现象。本文旨在从细胞和分子的角度全面分析癌症的耐药问题以及克服耐药的策略。证据获取:使用PubMed、Scopus、Web of Science等电子数据库,采用合适的关键词对相关文献进行系统检索。在回顾该领域的发展时,考虑了原始研究论文和二手文献。结果和结论:癌症耐药是一个普遍的挑战,导致许多治疗失败。尽管癌症治疗取得了显著进展,但对传统化疗药物和新型靶向药物的耐药性仍然是癌症治疗中一个巨大的障碍,导致癌症复发和死亡。事实上,大多数转移性癌症患者的治疗效果由于耐药而受到损害。耐药的多面性包括多种因素,如肿瘤异质性、生长动力学、免疫系统、微环境、物理障碍以及不可药物癌症驱动因素的出现。此外,药物内流/外排转运体、DNA修复机制和凋亡途径的改变进一步促进了耐药性,这可能表现为先天或后天特征,发生在治疗干预之前或之后。多种策略如联合治疗、靶向治疗、开发P-gp抑制剂、PROTACs和表观遗传调节剂来克服癌症耐药。耐药的管理由于患者和肿瘤的异质性以及癌症逃避治疗的能力而复杂化。进一步了解耐药性的潜在机制对于开发有效的治疗干预措施和改善患者预后至关重要。
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引用次数: 0
Empowering the pharmaceutical industry by revolutionizing education. 通过教育革命赋予制药行业权力。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-03 DOI: 10.1007/s40199-024-00547-6
Seyed Hossein Hajimiri, Fatemeh Soleymani

The pharmaceutical industry is poised for transformative advancements amid rapid technological developments and rising challenges. This editorial emphasizes the need to incorporate STEM (Science, Technology, Engineering, and Mathematics) disciplines into educational frameworks to prepare future professionals with the diverse skills essential for success. Effective collaboration between scientific knowledge, business acumen, and interdisciplinary teamwork is crucial for navigating the industry's evolving landscape. Innovations in education, such as e-learning, simulation-based training, and gamification, promote critical thinking, adaptability, and creativity in learners. Furthermore, partnerships between academia and the pharmaceutical sector-through internships, mentorships, and joint research-bridge theoretical knowledge with practical application. By adopting STEM-focused educational strategies and fostering strong industry-academic alliances, the next generation of pharmaceutical professionals will be equipped to tackle complex challenges and drive ongoing innovation and excellence within the industry.

在快速的技术发展和不断增加的挑战中,制药行业已准备好实现变革性进步。这篇社论强调了将STEM(科学、技术、工程和数学)学科纳入教育框架的必要性,以培养具有成功所必需的多样化技能的未来专业人士。科学知识、商业头脑和跨学科团队之间的有效协作对于引领行业不断发展的前景至关重要。教育创新,如电子学习、基于模拟的培训和游戏化,促进了学习者的批判性思维、适应能力和创造力。​通过采用以stem为重点的教育策略和培养强大的产业-学术联盟,下一代制药专业人员将具备应对复杂挑战的能力,并推动行业内的持续创新和卓越。
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引用次数: 0
Glatiramer acetate in situ forming gel, a new approach for multiple sclerosis treatment. 醋酸格拉替雷原位成形凝胶,治疗多发性硬化症的新方法。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-09-03 DOI: 10.1007/s40199-024-00532-z
Anahita Shobeirean, Hossein Attar, Reyhaneh Varshochian, Mohammad Amin Rezvanfar

Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

背景:醋酸格拉替雷(GA)是治疗多发性硬化症(MS)的常用药物,需要长期频繁注射以确保疗效。这往往会导致不良反应、患者不依从以及经济效益低下:本研究采用壳聚糖(CS)和透明质酸(HA)改性的热敏聚合物聚氧乙烯(poloxamer)制备 GA 原位成型缓释制剂,以克服频繁重复注射带来的问题,提高患者的依从性:方法:溶胶凝胶制剂是通过冷制法生产的,并通过实验设计进行了优化。方法:通过冷制法制备出溶胶-凝胶配方,并利用实验设计对其进行了优化,从凝胶化时间(GT)、流变行为、形态特性、检测和药物释放动力学等方面对最终产品进行了表征:结果:在最初的 24 小时内,GA 的体外释放速度非常快,但随后以 0.05 mg ml-1h-1 的较慢速度持续释放。皮下注射后的体内分析表明,与接受游离 GA 的小鼠相比,接受凝胶制剂治疗的小鼠在最初几天的 IL-5、IL-13 和尿酸(UA)水平较低。然而,10 天后,检测到的浓度明显升高,并继续缓慢增加:可以得出结论:所设计的热敏性溶胶-凝胶配方能够延长 GA 的疗效,可被视为治疗多发性硬化症的一种前景广阔的缓释配方。
{"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":"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<sup>-1</sup>h<sup>-1</sup>. 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":" ","pages":"649-664"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554603/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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DARU Journal of Pharmaceutical Sciences
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