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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-Robles, 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。
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引用次数: 0
Repurposing metformin as a potential anticancer agent using in silico technique. 利用硅学技术将二甲双胍重新用作潜在的抗癌药物。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-06-26 DOI: 10.1007/s40199-024-00523-0
Mona Mahfauz, Ozel Yuruker, Rasime Kalkan

Background: The focus on repurposing readily available, well-known drugs for new, creative uses has grown recently. One such medication is metformin, a drug commonly used to manage diabetes, which shows a favorable correlation between its use and lower cancer morbidity and death. Numerous investigations and clinical trials have been conducted to evaluate the possible application of metformin as an anticancer medication in light of this conclusion.

Objective: This study used 'pathway/gene-set analysis' Gene2drug, a resource for Gene Ontology (GO), and DepMap to determine whether metformin would be potentially advantageous for treating cancer.

Methods: A total of 1826 tumor cell lines were analyzed using the Drug Sensitivity (Primary Purposing Primary Screening) 19Q4 Tool.

Results: 9 genes from 402 genes, SGPL1, CXCR6, ATXN2L, LAMP3, RTN3, BTN2A1, FOXM1, NQO1, and L1TD1 in 1826 cancer cell line showed statistical sensitivity to metformin.

Conclusion: This in-silico study showed the sensitivity of specific cancer cell lines to metformin. Therefore, holding promises for metformin and tumor-targeted treatment strategies. It is recommended, however, to conduct further research into its potential effectiveness and mechanism of action.

背景:近来,人们越来越关注将现成的知名药物重新用于新的创造性用途。二甲双胍就是这样一种药物,它是一种常用于控制糖尿病的药物,其使用与降低癌症发病率和死亡率之间存在良好的相关性。根据这一结论,人们进行了大量调查和临床试验,以评估二甲双胍作为抗癌药物的应用可能性:本研究使用 "通路/基因组分析 "Gene2drug、基因本体(GO)资源和DepMap来确定二甲双胍是否对治疗癌症有潜在优势:方法:使用药物敏感性(初筛)19Q4 工具分析了 1826 个肿瘤细胞系:结果:在1826个肿瘤细胞系的402个基因中,SGPL1、CXCR6、ATXN2L、LAMP3、RTN3、BTN2A1、FOXM1、NQO1和L1TD1等9个基因对二甲双胍表现出统计学敏感性:该研究显示了特定癌细胞株对二甲双胍的敏感性。因此,二甲双胍和肿瘤靶向治疗策略大有可为。不过,建议对二甲双胍的潜在有效性和作用机制进行进一步研究。
{"title":"Repurposing metformin as a potential anticancer agent using in silico technique.","authors":"Mona Mahfauz, Ozel Yuruker, Rasime Kalkan","doi":"10.1007/s40199-024-00523-0","DOIUrl":"10.1007/s40199-024-00523-0","url":null,"abstract":"<p><strong>Background: </strong>The focus on repurposing readily available, well-known drugs for new, creative uses has grown recently. One such medication is metformin, a drug commonly used to manage diabetes, which shows a favorable correlation between its use and lower cancer morbidity and death. Numerous investigations and clinical trials have been conducted to evaluate the possible application of metformin as an anticancer medication in light of this conclusion.</p><p><strong>Objective: </strong>This study used 'pathway/gene-set analysis' Gene2drug, a resource for Gene Ontology (GO), and DepMap to determine whether metformin would be potentially advantageous for treating cancer.</p><p><strong>Methods: </strong>A total of 1826 tumor cell lines were analyzed using the Drug Sensitivity (Primary Purposing Primary Screening) 19Q4 Tool.</p><p><strong>Results: </strong>9 genes from 402 genes, SGPL1, CXCR6, ATXN2L, LAMP3, RTN3, BTN2A1, FOXM1, NQO1, and L1TD1 in 1826 cancer cell line showed statistical sensitivity to metformin.</p><p><strong>Conclusion: </strong>This in-silico study showed the sensitivity of specific cancer cell lines to metformin. Therefore, holding promises for metformin and tumor-targeted treatment strategies. It is recommended, however, to conduct further research into its potential effectiveness and mechanism of action.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"549-555"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450005","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
Structure-activity relationship of pharmacophores and toxicophores: the need for clinical strategy. 药理和毒理的结构-活性关系:临床策略的需要。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-06-27 DOI: 10.1007/s40199-024-00525-y
Saganuwan Alhaji Saganuwan

Objectives: Sometimes clinical efficacy and potential risk of therapeutic and toxic agents are difficult to predict over a long period of time. Hence there is need for literature search with a view to assessing cause of toxicity and less efficacy of drugs used in clinical practice.

Method: Hence literatures were searched for physicochemical properties, chemical formulas, molecular masses, pH values, ionization, receptor type, agonist and antagonist, therapeutic, toxic and structure-activity relationship of chemical compounds with pharmacophore and toxicophore, with a view to identifying high efficacious and relative low toxic agents. Inclusion criteria were manuscripts published on PubMed, Scopus, Web of Science, PubMed Central, Google Scholar among others, between 1960 and 2023. Keywords such as pharmacophore, toxicophore, structure-activity-relationship and disease where also searched. The exclusion criteria were the chemicals that lack pharmacophore, toxicophore and manuscripts published before 1960.

Results: Findings have shown that pharmacophore and toxicophore functional groups determine clinical efficacy and safety of therapeutics, but if they overlap therapeutic and toxicity effects go concurrently. Hence the functional groups, dose, co-administration and concentration of drugs at receptor, drug-receptor binding and duration of receptor binding are the determining factors of pharmacophore and toxicophore activity. Molecular mass, chemical configuration, pH value, receptor affinity and binding capacity, multiple pharmacophores, hydrophilic/lipophilic nature of the chemical contribute greatly to functionality of pharmacophore and toxicophore.

Conclusion: Daily single therapy, avoidance of reversible pharmacology, drugs with covalent adduct, maintenance of therapeutic dose, and the use of multiple pharmacophores for terminal diseases will minimize toxicity and improve efficacy.

目的:有时很难预测治疗和毒性药物的长期临床疗效和潜在风险。因此,有必要进行文献检索,以评估临床用药的毒性原因和疗效:因此,我们在文献中搜索了化合物的理化性质、化学式、分子质量、pH 值、电离、受体类型、激动剂和拮抗剂、治疗性、毒性以及与药理和毒理的结构-活性关系,以期找出高效和相对低毒的药物。纳入标准为 1960 年至 2023 年期间发表在 PubMed、Scopus、Web of Science、PubMed Central、Google Scholar 等网站上的手稿。此外,还搜索了药理、毒理、结构-活性-关系和疾病等关键词。排除标准是缺乏药效库、毒效库的化学物质以及 1960 年之前发表的稿件:研究结果表明,药效团和毒效团的功能基团决定着治疗药物的临床疗效和安全性,但如果它们重叠,治疗效果和毒性效果就会同时出现。因此,功能基团、剂量、联合用药和药物在受体上的浓度、药物与受体的结合以及受体结合的持续时间是药效团和毒效团活性的决定因素。分子质量、化学构型、pH 值、受体亲和力和结合能力、多重药性、化学品的亲水/亲脂性等因素对药性团和毒性团的功能性有很大影响:结论:日常单一疗法、避免使用可逆性药理、具有共价加成的药物、维持治疗剂量以及对终末期疾病使用多种药亲体将最大限度地减少毒性并提高疗效。
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引用次数: 0
Evaluating the effect of sodium alginate and sodium carboxymethylcellulose on pulmonary delivery of levofloxacin spray-dried microparticles. 评估海藻酸钠和羧甲基纤维素钠对左氧氟沙星喷雾干燥微颗粒肺部给药的影响。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-07-02 DOI: 10.1007/s40199-024-00526-x
Hanieh Alizadeh, Peyman Khoshhal, Maryam Sadat Mirmoeini, Kambiz Gilani

Background: Patients with cystic fibrosis commonly suffer from lung infections caused by Pseudomonas aeruginosa. Recently, the Levofloxacin (LVF) nebulizing solution (Quinsair®) has been prescribed for the antimicrobial management. The sustained-release (SR) dry powder formulation of LVF is a convenient alternative to Quinsair®. It has the potential to enhance patient convenience and decrease the likelihood of drug resistance over time.

Objective: In this paper, we set forth to formulate and evaluate the potential application of sodium alginate (SA) and sodium carboxymethylcellulose (SCMC) for sustained pulmonary delivery of LVF.

Methods: The spray-dried (SD) LVF microparticles were formulated using SCMC and SA along with L-leucine (Leu). The microparticles were analyzed in terms of particle size, morphology, x-ray diffraction (XRD), in-vitro drug release, and aerodynamic properties. Selected formulations were further proceeded to short-term stability test.

Results: The polymer-containing samples displayed process yield of 33.31%-39.67%, mean entrapment efficiency of 89% and volume size within the range of 2-5 μm. All the hydrogel microparticles were amorphous and exhibited rounded morphology with surface indentations. Formulations with a drug-to-excipient ratio of 50:50 and higher, showed a 24-h SR. The aerodynamic parameters were fine particle fraction and emitted dose percentage ranging between 46.21%-60.6% and 66.67%-87.75%, respectively. The short-term stability test revealed that the formulation with a 50:50 drug-to-excipient ratio, containing SA, demonstrated better physical stability.

Conclusion: The selected formulation containing SA has the potential to extend the release duration. However, further enhancements are required to optimize its performance.

背景:囊性纤维化患者通常会受到铜绿假单胞菌引起的肺部感染。最近,左氧氟沙星(LVF)雾化溶液(Quinsair®)被用于抗菌治疗。左氧氟沙星的缓释(SR)干粉制剂是 Quinsair® 的便捷替代品。它有可能为患者提供更多便利,并随着时间的推移降低产生耐药性的可能性:本文旨在配制和评估海藻酸钠(SA)和羧甲基纤维素钠(SCMC)在肺部持续给药 LVF 中的潜在应用:方法:使用羧甲基纤维素钠(SCMC)和海藻酸钠(SA)以及左旋亮氨酸(Leu)配制喷雾干燥(SD)LVF 微颗粒。对微粒的粒度、形态、X 射线衍射(XRD)、体外药物释放和空气动力学特性进行了分析。选定的配方还进一步进行了短期稳定性测试:结果:含聚合物的样品的加工产率为 33.31%-39.67%,平均包埋效率为 89%,体积大小在 2-5 μm 范围内。所有水凝胶微颗粒都是无定形的,呈圆形,表面有凹痕。药物与赋形剂之比为 50:50 或更高的制剂显示出 24 小时的 SR。空气动力学参数为细粒率和发射剂量百分比,分别为 46.21%-60.6% 和 66.67%-87.75% 。短期稳定性测试表明,药物与辅料比例为 50:50 且含有 SA 的制剂具有更好的物理稳定性:结论:所选含 SA 的制剂具有延长释放时间的潜力。然而,还需要进一步改进以优化其性能。
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引用次数: 0
Comparative evaluation of different oral iron salts in the management of iron deficiency anemia. 比较评估不同口服铁盐对缺铁性贫血的治疗效果。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-05-14 DOI: 10.1007/s40199-024-00517-y
Manoj A Suva, Pravin R Tirgar

Background: Anemia affects one-fourth of the world's population and is caused mostly by iron deficiency. Iron supplementation is the most essential strategy for preventing iron deficiency anemia. Conventional oral iron salts have many drawbacks such as poor absorption & bioavailability, and poor tolerability resulting in poor clinical outcomes.

Objective: To compare the effectiveness and safety of ferrous ascorbate, ferrous fumarate, ferrous bis-glycinate, and Sucrosomial iron in the management of iron deficiency anemia.

Method: The study is a retrospective observational clinical study comprising 260 subjects with hemoglobin between 7-10 g/dl. The patients were divided into four groups I, II, III, and IV, and received ferrous fumarate, ferrous ascorbate, ferrous bis-glycinate, and Sucrosomial iron respectively. Hematological profile and iron store indices were measured at baseline and month 3. One-way ANOVA followed by Tukey multiple comparison test was used to assess statistical significance (P < 0.05) using GraphPad Prism V.9.3.1 software.

Results: The observational study showed that hemoglobin levels were significantly increased in the ferrous ascorbate group (11.86 ± 0.09; P < 0.0001), ferrous fumarate group (11.72 ± 0.08; P < 0.0001), ferrous bis-glycinate group (11.69 ± 0.11; P = 0.0003) and Sucrosomial iron group (12.20 ± 0.1; P < 0.0001) compared to the baseline. The Sucrosomial iron-supplemented group showed significantly higher improvement in hemoglobin levels and serum ferritin levels compared to conventional oral iron salts (P < 0.05) with a better safety profile.

Conclusion: The Sucrosomial iron showed significantly higher improvement in hemoglobin levels and higher improvement in iron store indices parameters along with a good tolerability profile compared to other conventional oral iron salts.

背景:贫血影响着全球四分之一的人口,主要由缺铁引起。补铁是预防缺铁性贫血的最基本策略。传统的口服铁盐有许多缺点,如吸收和生物利用度差,耐受性差,导致临床效果不佳:比较抗坏血酸亚铁、富马酸亚铁、甘氨酸亚铁和蔗糖铁治疗缺铁性贫血的有效性和安全性:本研究是一项回顾性临床观察研究,共有 260 名血红蛋白在 7-10 g/dl 之间的患者参加。患者被分为 I、II、III 和 IV 四组,分别服用富马酸亚铁、抗坏血酸亚铁、甘氨酸亚铁和蔗糖铁。在基线和第 3 个月时测量血液学特征和铁储存指数,采用单因素方差分析和 Tukey 多重比较检验来评估统计学意义(P 结果):与其他传统口服铁盐相比,蔗糖铁对血红蛋白水平的改善幅度更大,对铁储存指标参数的改善幅度也更大,而且具有良好的耐受性。
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引用次数: 0
Royal jelly and its hormonal effects in breast cancer: a literature review. 蜂王浆及其对乳腺癌荷尔蒙的影响:文献综述。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-05-08 DOI: 10.1007/s40199-024-00513-2
Farzaneh Aavani, Roja Rahimi, Pouya Goleij, Hossein Rezaeizadeh, Roodabeh Bahramsoltani

Background: Breast cancer is the most common cancer in women which can be cured in most individuals with early-stage non-metastatic disease. Imbalance in estrogen signaling pathways and propagating levels of estrogens has important roles in breast cancer development. Targeting the estrogen receptor signaling pathway is linked to breast cancer treatment. Royal jelly is one of the bee products containing 10-hydroxy-2-decenoic acid, a structure similar to mammalian estrogen, allowing it to attach to estrogen receptors. It is considered as a general tonic and immunomodulator which may be helpful in reducing the side effects of cancer treatments. Currently, there are controversial data regarding the pros and cons of royal jelly in cancer. Here we provide an overview of the effects of royal jelly on sex hormones and its possible role in breast cancer.

Methods: Electronic databases including PubMed, Scopus, and Web of Science were searched with the search terms royal jelly, cancer, and sexual hormones. All preclinical and clinical studies regarding the hormonal effects of royal jelly were included.

Results: According to the collected preclinical data, consumption of royal jelly at daily doses below 200 mg/kg can be useful to decrease the risk of breast cancer since it reduces the serum level of estrogen; whereas increases progesterone, which subsequently decreases the expression of ERs on the ER-positive cells.

Conclusion: Future clinical studies are essential to confirm the safe dose of royal jelly as an adjuvant therapy in breast cancer.

背景:乳腺癌是女性最常见的癌症,大多数早期非转移性乳腺癌患者可以治愈。雌激素信号通路的失衡和雌激素水平的升高在乳腺癌的发展中起着重要作用。针对雌激素受体信号通路的治疗与乳腺癌的治疗有关。蜂王浆是蜂产品之一,含有10-羟基-2-癸烯酸,其结构与哺乳动物的雌激素相似,可附着在雌激素受体上。蜂王浆被认为是一种综合滋补品和免疫调节剂,可能有助于减轻癌症治疗的副作用。目前,关于蜂王浆对癌症的利弊还存在争议。在此,我们概述了蜂王浆对性激素的影响及其在乳腺癌中可能发挥的作用:方法:以蜂王浆、癌症和性激素为检索词,对PubMed、Scopus和Web of Science等电子数据库进行检索。所有有关蜂王浆荷尔蒙作用的临床前和临床研究均被纳入:结果:根据收集到的临床前数据,每天食用低于200毫克/千克剂量的蜂王浆可降低罹患乳腺癌的风险,因为蜂王浆可降低血清中的雌激素水平,同时增加孕酮,从而减少ER阳性细胞中ERs的表达:未来的临床研究对于确定蜂王浆作为乳腺癌辅助疗法的安全剂量至关重要。
{"title":"Royal jelly and its hormonal effects in breast cancer: a literature review.","authors":"Farzaneh Aavani, Roja Rahimi, Pouya Goleij, Hossein Rezaeizadeh, Roodabeh Bahramsoltani","doi":"10.1007/s40199-024-00513-2","DOIUrl":"10.1007/s40199-024-00513-2","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most common cancer in women which can be cured in most individuals with early-stage non-metastatic disease. Imbalance in estrogen signaling pathways and propagating levels of estrogens has important roles in breast cancer development. Targeting the estrogen receptor signaling pathway is linked to breast cancer treatment. Royal jelly is one of the bee products containing 10-hydroxy-2-decenoic acid, a structure similar to mammalian estrogen, allowing it to attach to estrogen receptors. It is considered as a general tonic and immunomodulator which may be helpful in reducing the side effects of cancer treatments. Currently, there are controversial data regarding the pros and cons of royal jelly in cancer. Here we provide an overview of the effects of royal jelly on sex hormones and its possible role in breast cancer.</p><p><strong>Methods: </strong>Electronic databases including PubMed, Scopus, and Web of Science were searched with the search terms royal jelly, cancer, and sexual hormones. All preclinical and clinical studies regarding the hormonal effects of royal jelly were included.</p><p><strong>Results: </strong>According to the collected preclinical data, consumption of royal jelly at daily doses below 200 mg/kg can be useful to decrease the risk of breast cancer since it reduces the serum level of estrogen; whereas increases progesterone, which subsequently decreases the expression of ERs on the ER-positive cells.</p><p><strong>Conclusion: </strong>Future clinical studies are essential to confirm the safe dose of royal jelly as an adjuvant therapy in breast cancer.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"745-760"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876122","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
Ameliorative effect of Melatonin on 5-Fluorouracil-induced reproductive toxicity in male rats. 褪黑素对 5-氟尿嘧啶诱导的雄性大鼠生殖毒性的改善作用
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-09-23 DOI: 10.1007/s40199-024-00537-8
Darya Almasi, Sohrab Kazemi, Mohammad Hossien Asghari, Seyed Mohammad Hosseini, Ali Akbar Moghadamnia

5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic agent that can cause oxidative stress and complications in normal organs, including the reproductive system. This study was conducted to investigate the effect of melatonin (MEL) on 5-FU-induced reproductive toxicity in male rats. Male Wistar rats weighing 180 ± 20 g were divided into five groups: control, 5-FU (50 mg/kg), 5-FU + MEL (2.5, 5 & 10 mg/kg). The testes and prostates were removed, and histopathological aspects, biochemical markers, and gene expression were investigated. The effect of 5-FU on the normal TM4 cell line (murine testicular Sertoli line) and co-treatment of 5-FU and MEL were studied using MTT assay. Results showed that MEL prevented cell death in the TM4 cell line induced by 5-FU. MEL also reduced edema, hyperemia, and vacuolization in testis and prostate tissues induced by 5-FU. Additionally, MEL increased the activity of antioxidant enzymes and reduced the levels of MDA (p < 0.0001) and MPO (p < 0.0001). The levels of testosterone (p < 0.01) and the number of spermatocytes and spermatogonia (p < 0.0001) were increased in groups receiving 5-FU with MEL compared to 5-FU alone. The prostate-specific antigen (PSA) level in prostate samples was lower in the groups receiving 5-FU with MEL compared to the 5-FU group. Furthermore, the genes expression of COX-2 and TNF-α in testis tissues was reduced in the presence of MEL. in conclusion, the antioxidant property of MEL can protect the male reproductive system against 5-FU toxicity, as evidenced by the improved histopathological and biochemical parameters, as well as the reduced gene expression of COX-2 and TNF- α genes.

5-氟尿嘧啶(5-FU)是一种抗代谢化疗药物,可引起正常器官(包括生殖系统)的氧化应激和并发症。本研究旨在探讨褪黑素(MEL)对 5-FU 诱导的雄性大鼠生殖毒性的影响。体重为 180 ± 20 g 的雄性 Wistar 大鼠被分为五组:对照组、5-FU(50 mg/kg)组、5-FU + MEL(2.5、5 和 10 mg/kg)组。切除睾丸和前列腺,对组织病理学、生化指标和基因表达进行研究。使用 MTT 试验研究了 5-FU 对正常 TM4 细胞系(小鼠睾丸 Sertoli 细胞系)的影响以及 5-FU 和 MEL 联合治疗的影响。结果表明,MEL能防止5-FU诱导的TM4细胞系的细胞死亡。MEL 还能减轻 5-FU 引起的睾丸和前列腺组织水肿、充血和空泡化。此外,MEL 还提高了抗氧化酶的活性,降低了 MDA 的水平(p
{"title":"Ameliorative effect of Melatonin on 5-Fluorouracil-induced reproductive toxicity in male rats.","authors":"Darya Almasi, Sohrab Kazemi, Mohammad Hossien Asghari, Seyed Mohammad Hosseini, Ali Akbar Moghadamnia","doi":"10.1007/s40199-024-00537-8","DOIUrl":"10.1007/s40199-024-00537-8","url":null,"abstract":"<p><p>5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic agent that can cause oxidative stress and complications in normal organs, including the reproductive system. This study was conducted to investigate the effect of melatonin (MEL) on 5-FU-induced reproductive toxicity in male rats. Male Wistar rats weighing 180 ± 20 g were divided into five groups: control, 5-FU (50 mg/kg), 5-FU + MEL (2.5, 5 & 10 mg/kg). The testes and prostates were removed, and histopathological aspects, biochemical markers, and gene expression were investigated. The effect of 5-FU on the normal TM4 cell line (murine testicular Sertoli line) and co-treatment of 5-FU and MEL were studied using MTT assay. Results showed that MEL prevented cell death in the TM4 cell line induced by 5-FU. MEL also reduced edema, hyperemia, and vacuolization in testis and prostate tissues induced by 5-FU. Additionally, MEL increased the activity of antioxidant enzymes and reduced the levels of MDA (p < 0.0001) and MPO (p < 0.0001). The levels of testosterone (p < 0.01) and the number of spermatocytes and spermatogonia (p < 0.0001) were increased in groups receiving 5-FU with MEL compared to 5-FU alone. The prostate-specific antigen (PSA) level in prostate samples was lower in the groups receiving 5-FU with MEL compared to the 5-FU group. Furthermore, the genes expression of COX-2 and TNF-α in testis tissues was reduced in the presence of MEL. in conclusion, the antioxidant property of MEL can protect the male reproductive system against 5-FU toxicity, as evidenced by the improved histopathological and biochemical parameters, as well as the reduced gene expression of COX-2 and TNF- α genes.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"675-687"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281698","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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