Medicine in Drug Discovery最新文献

{"title":"Unlocking the therapeutic capabilities of GPCR in the treatment of ischemic stroke: A translational literature","authors":"Girish B S Pharm.D,&nbsp;Nikitha B S Pharm.D,&nbsp;Roopa K Pharm.D,&nbsp;Meghana C S Pharm.D,&nbsp;Srinivasan R M.Pharm, PhD","doi":"10.1016/j.medidd.2024.100197","DOIUrl":"10.1016/j.medidd.2024.100197","url":null,"abstract":"<div><p>GPCRs are a class of membrane proteins that are essential to signal transduction, and this is a vital process in many different physiologies. The significant mortality rate and widespread occurrence of stroke highlight the need to accelerate the research to develop viable treatment agents. A promising prospect for the development of new treatment approaches is the increasing comprehension of the pathophysiology of stroke and the crucial roles played by GPCRs. Because of the blood clot, the glial cells’ vascular supply is abruptly cut off, which sets off a series of events that include inflammation and neuronal damage and ultimately lead to cell death. Numerous therapeutic treatments, including thrombolytic agents like tissue plasminogen activator and urokinase, have been discovered as potential neuroprotective medicines; however, their use is restricted because of the modest therapeutic window. Accepting that GPCRs are the pertinent factors in ischemic stroke, we explore the potential medicinal promise of GPCR-targeted treatments and the shortcomings that ought to be resolved in order to translate these discoveries to clinical cases.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000228/pdfft?md5=7ea1babb292d6f267fc89fefc770927a&pid=1-s2.0-S2590098624000228-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142083841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The psychological distress associated with type 2 diabetes mellitus represents an unmet need for drug discovery","authors":"S. Akshatha,&nbsp;Uday B. Nayak","doi":"10.1016/j.medidd.2024.100196","DOIUrl":"10.1016/j.medidd.2024.100196","url":null,"abstract":"<div><p>Non-adherence to antidiabetic medication remains the major factor contributing to poor clinical outcomes among patients with type 2 diabetes mellitus (T2DM). This study was designed to investigate the cross-sectional association between psychological distress and medication adherence in T2DM patients. Participants were 100 adults with T2DM from a teaching hospital in South India. Psychological distress was assessed using the 12-item General Health Questionnaire (GHQ-12) and the 8-item Morisky Medication Adherence Scale (MMAS-8) was used to assess medication adherence. This study demonstrated that a high proportion of patients (70 %) with T2DM experience psychological distress. Higher self-reported distress was the strongest independent predictor of medication non-adherence (β = −0.1145; P=0.0002). The study highlights that psychological distress in T2DM patients meets important drug discovery criteria such as unmet medical need, disease prevalence, and success probability. Understanding the biological mechanisms that underpin psychological distress would aid in the development of mechanism-based therapies. Better integration of medical and psychosocial treatments in general medical practice may be important to improve treatment adherence and reduce disparities in chronic disease care.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"23 ","pages":"Article 100196"},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000216/pdfft?md5=84ca60766df327a2a797407c7cac8d77&pid=1-s2.0-S2590098624000216-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142021477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent developments in receptor tyrosine kinase inhibitors: A promising mainstay in targeted cancer therapy","authors":"Rahul Kumar ,&nbsp;Harsh Goel ,&nbsp;Raghu Solanki ,&nbsp;Laxminarayan Rawat ,&nbsp;Saba Tabasum ,&nbsp;Pranay Tanwar ,&nbsp;Soumitro Pal ,&nbsp;Akash Sabarwal","doi":"10.1016/j.medidd.2024.100195","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100195","url":null,"abstract":"<div><p>During the past two decades, significant advances have been made in the discovery and development of targeted inhibitors aimed at improving the survival rates of cancer patients. Among the multitude of potential therapeutic targets identified thus far, Receptor Tyrosine Kinases (RTKs) are of particular importance. Dysregulation of RTKs has been implicated in numerous human diseases, particularly cancer, where aberrant signaling pathways contribute to disease progression. RTKs have a profound impact on intra and intercellular communication, and they also facilitate post-translational modifications, notably phosphorylation, which intricately regulates a multitude of cellular processes. Prolonged phosphorylation or the disruption of kinase regulation may lead to significant alterations in cell signaling. The emergence of small molecule kinase inhibitors has revolutionized cancer therapy by offering a targeted and strategic approach that surpasses the efficacy of traditional chemotherapeutic drugs. Over the last two decades, a plethora of targeted inhibitors have been identified or engineered and have undergone clinical evaluation to enhance the survival rates of cancer patients. In this review, we have compared the expression of different RTKs, including Met, KDR/VEGFR2, EGFR, BRAF, BCR, and ALK across different cancer types in TCGA samples. Additionally, we have summarized the recent development of small molecule inhibitors and their potential in treating various malignancies. Lastly, we have discussed the mechanisms of acquired therapeutic resistance with a focus on kinase inhibitors in EGFR mutant and ALK-rearranged non-small cell lung cancer and BCR-ABL positive chronic myeloid leukemia.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"23 ","pages":"Article 100195"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000204/pdfft?md5=90e864d311e6f6cbf02a7d7750d65e67&pid=1-s2.0-S2590098624000204-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141541796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing nitrofurantoin as a stimulant of fibroblast extracellular matrix repair for the treatment of emphysema","authors":"Mathew N. Leslie ,&nbsp;Zara Sheikh ,&nbsp;Dikaia Xenaki ,&nbsp;Brian G. Oliver ,&nbsp;Paul M. Young ,&nbsp;Daniela Traini ,&nbsp;Hui Xin Ong","doi":"10.1016/j.medidd.2024.100194","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100194","url":null,"abstract":"<div><p>Emphysema is a respiratory disease that causes the progressive loss of lung extracellular matrix (ECM) organisation, subsequently undermining lung integrity and reducing lung function. Fibroblasts must constantly repair damage to the lungs to preserve lung health, however, fibroblast ECM repair is reduced during emphysema, causing ECM damage to outweigh fibroblast ECM maintenance. Current treatments for emphysema fail to address the root causes of emphysematous progression, highlighting the need for novel methods of treating emphysema. Nitrofurantoin is a broad-spectrum antibiotic indicated for the treatment of urinary tract infections that also displays potential as a novel avenue of emphysema treatment. Nitrofurantoin is known to potentially cause fibrotic effects that could be repurposed to increase fibroblast repair and outweigh the progressive ECM damage of the emphysematous lung. Therefore, this study examined the effects of nitrofurantoin treatment on primary human lung fibroblasts derived from emphysema patients to determine if the drug holds potential as a novel treatment for emphysema. Nitrofurantoin was shown to stimulate migration and alter fibroblast morphology by increasing cell area and reducing roundness, suggesting that it could induce an ECM-repair primed phenotype in fibroblasts. Interestingly, nitrofurantoin treatment did not alter collagen-IV, perlecan, periostin or tenascin-C deposition, though fibronectin deposition was significantly upregulated at a higher dosage (20 μg/mL). This study highlighted the nitrofurantoin induced changes to fibroblast motility and morphology that facilitate ECM repair. Thus, nitrofurantoin induced pulmonary fibrosis could be caused by a change in cell phenotype that subsequently upregulates ECM repair, indicating its potential as a treatment for emphysema.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"23 ","pages":"Article 100194"},"PeriodicalIF":0.0,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000198/pdfft?md5=e01ff09770a2b573a87f8957214ffc30&pid=1-s2.0-S2590098624000198-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the kinetic features of orexin receptor antagonists at orexin receptors, transduction systems and receptor binding","authors":"Daniel Hoyer ,&nbsp;Laura H. Jacobson","doi":"10.1016/j.medidd.2024.100190","DOIUrl":"10.1016/j.medidd.2024.100190","url":null,"abstract":"<div><p>Orexin receptor antagonists are on the market or under development for the treatment of insomnia and a number of other neuropsychiatric disorders. Currently, suvorexant, lemborexant and daridorexant, three dual orexin receptor antagonists (DORAs) have received market approval by regulatory authorities in the USA, Australia, Europe and/or Japan for the treatment of insomnia. More DORAs and Selective Orexin Receptor Antagonists (SORAs) in addition to orexin receptor agonists are in various stages of preclinical and clinical development: for instance, 1SORAs (selective orexin 1 receptor antagonists) are being developed for the treatment of anxiety, panic, eating disorders, whereas 2SORAs (selective orexin 2 receptor antagonists) are in late clinical stage for the treatment of insomnia and insomnia-related depression. On the other hand, selective orexin 2 receptor agonists are in clinical trials for the treatment of narcolepsy with (NT1) or without cataplexy (NT2) and other aspects of extreme day time sleepiness.</p><p>Traditionally, the medium to high throughput screening procedures used to screen / characterize orexin receptor antagonists or agonists (and for that matter ligands acting on a variety of potential drug targets), frequently ignore two aspects of new drugs candidates: possible functional selectivity (biased agonism or antagonism) and intrinsic receptor-ligand kinetic properties (i.e. association and dissociation features at the target level), since most screening protocols are conducted under short incubation time conditions with usually a single functional readout. Here, we report on strategies to characterise orexin receptor ligands (agonists or antagonists) in radioligand binding and calcium mobilization assays (e.g. using the FLIPR ® /Fluorescent Imaging Plate Reader assay) and for a few select DORAs, on ERK activation. We studied clinically effective and/or tool orexin receptor antagonists (almorexant, suvorexant, filorexant, SB-649868, MK1064…), which have been or are being evaluated in clinical trials or are on the market, in these signalling pathways with an emphasis on kinetics. Thus, we investigated calcium mobilization and pERK elevation triggered by orexin A (OXA) in HEK293 cells stably transfected with human OX₁R or OX₂R. We confirmed that the ligands behave as antagonists in either assay. Most ligands do not show significant functional selectivity between the two pathways, except MK-1064, which inhibits calcium mobilization about 35 times more potently than ERK phosphorylation. We also estimated the kinetic properties of the antagonists in radioligand binding, calcium mobilization and pERK assays. The results of radioligand binding and calcium mobilization assays indicate consistently that several of the tested antagonists bind to/dissociate from either or the two orexin receptors very slowly, with equilibrium reached only after several hours. Thus, SB-649868 is a very slow binder at the OX<su","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100190"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000150/pdfft?md5=b1feee5aa6e995c5dbe01943f9c05654&pid=1-s2.0-S2590098624000150-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141136060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “Potent anti-Toxoplasma gondii activity of 4-chlorophenylthioacetone-derived thiosemicarbazones: Involvement of CCR2 and CCR5 receptors and 5-lipoxygenase in the mode of action” [Med. Drug Discovery 18 (2023) 100157]","authors":"Rayane Aparecida Nonato Rabelo ,&nbsp;Diego Rodney Rodrigues de Assis ,&nbsp;Alexandre Almeida Oliveira ,&nbsp;César Luís Nascimento Barbosa ,&nbsp;Rafaela das Dores Pereira ,&nbsp;Ricardo Wagner de Almeida Vitor ,&nbsp;Wiliam César Bento Régis ,&nbsp;Mauro Martins Teixeira ,&nbsp;Heloísa Beraldo ,&nbsp;Fabiana Simão Machado","doi":"10.1016/j.medidd.2024.100192","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100192","url":null,"abstract":"","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100192"},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000174/pdfft?md5=7f508b00f71d22603d13481fdba1b2b8&pid=1-s2.0-S2590098624000174-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141067733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose aspirin increases olfactory sensitivity in association with enhanced neurogenesis and reduced activity of AChE in the experimental aging mice","authors":"Jemi Feiona Vergil Andrews ,&nbsp;Divya Bharathi Selvaraj ,&nbsp;Abhinav Bhavani Radhakrishnan ,&nbsp;Mahesh Kandasamy","doi":"10.1016/j.medidd.2024.100191","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100191","url":null,"abstract":"<div><p>This study examined the effect of aspirin on olfactory discrimination and neurogenesis in experimental aging mice. The results from the buried food test (BFT) and odour preference test (OPT) indicated that aspirin treatment enhanced the olfactory functions in the experimental animals. The immunohistochemical assessment revealed increased amounts of doublecortin (DCX)-positive immature neurons and bromodeoxyuridine (BrdU)/neuronal nuclei (NeuN) double-positive new neurons in the olfactory bulb (OB) of aspirin-treated animals compared to the control group. Besides, aspirin treatment resulted in a decreased number of ionized calcium-binding adaptor molecule (Iba)-1 positive microglia, a main cellular element of neuroinflammation in the brain compared to the control group. In addition, the increased activities of key antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in OB of the aspirin-treated mice were evident. Acetylcholinesterase (AChE) is a key enzyme that hydrolyses acetylcholine (ACh), an important neurotransmitter, involved in cognition, and olfaction. While the enhanced activity of AChE has been linked to the severity of dementia and OB defects, the biochemical assessments indicated reduced activity of AChE in OB-derived homogenates of the aspirin-treated experimental animals than that of the control group. Taken together, this study validates the proneurogenic, cholinergic, and anti-neuroinflammatory properties of aspirin in the OB which can be considered in boosting neural regeneration and management of olfactory deficits in aging and various disorders.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100191"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000162/pdfft?md5=d6da6542d0e2d61ba6fea2736a369852&pid=1-s2.0-S2590098624000162-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140894878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy: Playing an important role in diabetes and its complications","authors":"Ning Wang ,&nbsp;Yinghua Zhou ,&nbsp;Ebenezeri Erasto Ngowi ,&nbsp;Aijun Qiao","doi":"10.1016/j.medidd.2024.100188","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100188","url":null,"abstract":"<div><p>Diabetes, a chronic disease significantly affects peoples’ health and quality of life. It is a major contributor of severe health complications, such as blindness, kidney failure, heart attacks, strokes, and lower limb amputations. Autophagy is a complex cellular process regulated by specific genes. It is responsible for degrading intracellular proteins and organelles within lysosomes, a process which is crucial for maintaining internal cellular balance and clearing damaged or obsolete cellular components. In the context of diabetes, autophagy plays a key role in maintaining blood glucose homeostasis, particularly through the regulation of insulin secretion and sensitivity. Additionally, autophagy aids in preserving the survival and function of pancreatic beta (β)-cells by eliminating harmful proteins within these cells, which is vital for the prevention and treatment of diabetes. Despite the key role autophagy plays in these aspects, its exact mechanisms and effects in diabetes are still complex and not fully understood. Therefore, further research is needed to deeply explore the specific mechanisms and potential therapeutic applications of autophagy in diabetes. This review explores autophagy's classification, mechanisms, role in diabetic pathogenesis and complications, and its potential in treatment strategies of disease.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100188"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000137/pdfft?md5=9de6380dcfdce6966162377ed09f1f05&pid=1-s2.0-S2590098624000137-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140548813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanomedicine-based drug delivery strategies for the treatment of atherosclerosis","authors":"Yongfang Lin ,&nbsp;Ruibo Lin ,&nbsp;Han-Bin Lin ,&nbsp;Shiyang Shen","doi":"10.1016/j.medidd.2024.100189","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100189","url":null,"abstract":"<div><p>Atherosclerosis, a highly prevalent cardiovascular disease, has significantly contributed to morbidity and mortality worldwide. Despite the availability of various treatment options in clinical practice, complete reversal of the atherosclerotic pathological process remains challenging. Traditional anti-arteriosclerosis drugs often suffer from poor solubility, limited targeting ability and obvious adverse effects. Additionally, novel therapeutics such as genetic and protein-based drugs inherently suffer from instability issues, thereby compromising their actual curative efficacy and impeding further clinical application. Recently, nanomedicine-based drug delivery strategies have emerged as promising approaches for treating atherosclerosis due to their ability to specifically transport various drugs to target cells, microstructures and specific molecules within lesion sites. These advanced features enhance drug properties and bioavailability while minimizing off-target effects. Moreover, numerous studies have demonstrated that nanomedicine not only inhibits plaque progression but also reduces lesional areas and eventually reverses atherosclerosis. The utilization of nanomedicine is considered an important therapeutic tactic for further mitigating residual risks associated with atherosclerosis. This review provides a comprehensive overview of emerging nanomedicine-based strategies for targeted delivery of anti-atherosclerosis drugs, elucidating their distinct mechanisms and highlighting their remarkable efficacy in combating atherosclerosis. Additionally, critical challenges and future perspectives associated with the development and application of anti-arteriosclerosis nanomedicine are thoroughly discussed.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100189"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000149/pdfft?md5=b0905b911586f9255095ff830b97cd8e&pid=1-s2.0-S2590098624000149-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140553935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lesson from nature: Zataria multiflora nanostructured lipid carrier topical gel formulation against Candida-associated onychomycosis, a randomized double-blind placebo-controlled clinical trial","authors":"Maryam Moazeni ,&nbsp;Hamidreza Kelidari ,&nbsp;Yaser Nasirzadehfard ,&nbsp;Tahereh Shokohi ,&nbsp;Behrad Roohi ,&nbsp;Zohreh Hajheidari ,&nbsp;Armaghan Kazeminejad ,&nbsp;Shima Parsay ,&nbsp;Kofi Asare-Addo ,&nbsp;Ali Nokhodchi","doi":"10.1016/j.medidd.2024.100187","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100187","url":null,"abstract":"<div><h3>Purpose</h3><p>The increasing resistance to onychomycosis treatment globally is a major concern as it results in treatment failures. This research aimed to investigate the effectiveness of incorporating nanostructured lipid carriers (NLCs) in a gel formulation for treating mild to moderate <em>Candida</em>-associated onychomycosis using <em>Zataria multiflora</em> (Zt) essential oils.</p></div><div><h3>Methods</h3><p>The characteristics of <em>Zataria multiflora</em>-loaded nanostructured lipid carriers (Zt-NLCs) were validated using a carbopol gel (1 % w/w). <em>In vitro</em> tests were conducted using CLSI M60 standards to evaluate the susceptibility of ten commonly encountered dermatophyte species to antifungal agents. A clinical study was conducted involving 40 volunteers randomly assigned to two groups: one receiving the Zt-NLCs gel and the other receiving a placebo, using a double-blind, placebo-controlled design. The objective was to assess clinical manifestations and mycological findings after topical application for 2 and 4 weeks. The causative agents' species were identified using a PCR-RFLP method.</p></div><div><h3>Results</h3><p>The preparation of Zt-NLCs gel resulted in a uniform suspension of spherical nanoparticles with favourable characteristics and no cytotoxic effects. Zt-NLCs demonstrated significant inhibitory effects on fungal growth and effectively improved clinical and mycological criteria in comparison to the placebo group (p &lt; 0.005), even after 2 weeks of treatment. The <em>C. albicans</em> complex was recognized as the predominant species isolated from the patients using PCR-RFLP.</p></div><div><h3>Conclusion</h3><p>The administration of Zt-NLCs gel for two weeks showed significant efficacy in disease management, as reported by both dermatologists and mycologists and therefore shows its potential use as a treatment against <em>Candidal</em> onychomycosis.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100187"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000125/pdfft?md5=d7a1baaf0ba6618dfae2bc5073b9b1a7&pid=1-s2.0-S2590098624000125-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140540763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}