Biomedicine & Pharmacotherapy最新文献

{"title":"Effects of sacubitril/valsartan on cardiac remodeling in heart failure with reduced ejection fraction: An integrated study of molecular biomarkers and imaging techniques","authors":"Ainhoa Robles-Mezcua ,&nbsp;James L. Januzzi ,&nbsp;Francisco Javier Pavón-Morón ,&nbsp;Jorge Rodríguez-Capitán ,&nbsp;Miguel A. López-Garrido ,&nbsp;Concepción Cruzado-Álvarez ,&nbsp;María Robles-Mezcua ,&nbsp;Mario Gutiérrez-Bedmar ,&nbsp;David Couto-Mallón ,&nbsp;Eloy C. Rueda-Calle ,&nbsp;Manuel Barreiro-Pérez ,&nbsp;Pedro L. Sánchez ,&nbsp;Juan José Gómez-Doblas ,&nbsp;Manuel F. Jiménez-Navarro ,&nbsp;José M. García-Pinilla","doi":"10.1016/j.biopha.2025.117874","DOIUrl":"10.1016/j.biopha.2025.117874","url":null,"abstract":"<div><div>Treatment of heart failure and reduced ejection fraction (HFrEF) using angiotensin receptor-neprilysin inhibitor demonstrates beneficial effects on cardiac remodeling (CR). We assessed the impact of sacubitril/valsartan on the concentrations of HF biomarkers in relation to parameters of CR using imaging techniques in patients with HFrEF. In a prospective single-center open-label study, 68 patients with symptomatic HFrEF were treated with sacubitril/valsartan and followed-up every three months for 12 months. Soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin I (hs-cTnI) were measured in blood samples. Additionally, echocardiography and cardiac magnetic resonance imaging (cMRI) were performed to assess heart structural and functional changes. Following treatment initiation, follow-up visits revealed an improved NYHA functional class in these patients, alongside significant decreases in all circulating biomarkers, increases in left ventricular ejection fraction (LVEF), and reductions in volume- and diameter-related LV parameters. Sustained gradual decreases in sST2 concentrations over time correlated with NT-proBNP concentrations (rho=+0.26, <em>P</em> &lt; 0.001). Both biomarkers were inversely correlated with LVEF, and positively correlated with volume- and diameter-related LV parameters from echocardiography and cMRI. However, NT-proBNP concentrations exhibited stronger correlations with these LV parameters and were associated with the number of LV segments showing fibrosis, unlike sST2. Sacubitril/valsartan treatment in HFrEF leads to reduced sST2 and NT-proBNP concentrations with distinct decreasing curves, which are linked to reverse CR through LV-related parameters. In contrast to sST2, NT-proBNP is also associated with fibrosis, suggesting that both biomarkers unveil distinct mechanisms during CR in patients treated with sacubitril/valsartan.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117874"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statins and non-alcoholic fatty liver disease: A concise review","authors":"Evelyn Nunes Goulart da Silva Pereira,&nbsp;Rafaela Luiza Costa Franco,&nbsp;Rafaele Dantas Cruz dos Santos,&nbsp;Anissa Daliry","doi":"10.1016/j.biopha.2024.117805","DOIUrl":"10.1016/j.biopha.2024.117805","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is a common hepatic manifestation of metabolic syndrome affecting 20–30 % of the adult population worldwide. This disease, which includes simple steatosis and non-alcoholic steatohepatitis, poses a significant risk for cardiovascular and metabolic diseases. Lifestyle modifications are crucial in the treatment of NAFLD; however, patient adherence remains challenging. As there is no specific treatment, drug repositioning is being researched as an alternative strategy. Statins, which are known for their cholesterol-lowering effects, are considered potential interventions for NAFLD. This review aimed to present the current understanding of the effects of statins on liver physiology in the context of NAFLD. The pathophysiology of NAFLD includes steatosis, inflammation, and fibrosis, which are exacerbated by dyslipidemia and insulin resistance. Statins, which inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, have pleiotropic effects beyond cholesterol-lowering and affect pathways related to inflammation, fibrogenesis, oxidative stress, and microcirculation. Although clinical guidelines support the use of statins for dyslipidemia in patients with NAFLD, more studies are needed to demonstrate their efficacy in liver disease. This comprehensive review serves as a foundation for future studies on the therapeutic potential of statins in NAFLD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117805"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Illudin S inhibits p53-Mdm2 interaction for anticancer efficacy in colorectal cancer” [Biomed. Pharmacother. 182 (2025) 117795]","authors":"Yoonsuk Lee ,&nbsp;Yun Young Lee ,&nbsp;Jinyoung Park ,&nbsp;Anna Maksakova ,&nbsp;Donghyuk Seo ,&nbsp;Jisun Kim ,&nbsp;Ji Eun Yeom ,&nbsp;Yewon Kim ,&nbsp;Cheol-Hwi Kim ,&nbsp;Rhim Ryoo ,&nbsp;Se-Na Kim ,&nbsp;Juwon Park ,&nbsp;Wooram Park ,&nbsp;Tae-Hyung Kim ,&nbsp;Young Bin Choy ,&nbsp;Chun Gwon Park ,&nbsp;Ki Hyun Kim ,&nbsp;Wonhwa Lee","doi":"10.1016/j.biopha.2025.117810","DOIUrl":"10.1016/j.biopha.2025.117810","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117810"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-delivery of curcumin-resveratrol-carnosic acid complex promotes neurogenesis and cognitive recovery in a rodent model of repeated mild traumatic brain injury","authors":"Mohind C. Mohan ,&nbsp;A.S. Anjana ,&nbsp;T.A. Hilmi Jaufer ,&nbsp;Ayswaria Deepti ,&nbsp;I.M. Krishnakumar ,&nbsp;P.S. Baby Chakrapani","doi":"10.1016/j.biopha.2025.117818","DOIUrl":"10.1016/j.biopha.2025.117818","url":null,"abstract":"<div><div>Repeated traumatic brain injury has grown in importance as sports-related injuries have increased. Repetitive mild TBI (rmTBI) increases the risk of developing neurodegenerative diseases such as Alzheimer’s and Parkinson's diseases, as well as chronic comorbidities like PTSD, depression, substance abuse and neuroendocrine functions. However, no effective therapeutic strategies have been reported for the effective management of TBI. Herein, we examined the effectiveness of co-delivery of the phytonutrients curcumin, <em>trans</em>-resveratrol, and carnosic acid as a bioavailable complex (CGM+) in managing rmTBI in the rodent model. The rats were randomly assigned to sham, rmTBI, and CGM+ (300 mg/kg b.wt.) groups for a total of 21 days. On Days 6 and 7, all animals, except those in the sham group, were subjected to repeated mild traumatic brain injury (rmTBI). The CGM+ group received supplementation throughout the 21 days, while the other groups received a vehicle. Neurological severity score (NSS) was assessed 24 h after the last injury, and behavioral tests were completed within 14 days post-injury. Samples for the biochemical analysis were collected after euthanasia. CGM+ supplementation significantly decreased the sensory-motor deficits associated with rmTBI. Following TBI, the CGM+ group demonstrated enhanced memory and low-stress levels. Furthermore, CGM+ has been shown to modulate neurotransmitter levels and promote neurogenesis. The biochemical and molecular analysis revealed that CGM+ promotes recovery following rmTBI by modulating mitochondrial bioenergetics and BDNF pathways. The findings indicate that CGM+ can be used to manage cognitive and sensory-motor defects caused by rmTBI, such as in the case of sports injuries.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117818"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HEBE: A novel chimeric chronokine for ameliorating memory deficits in Alzheimer’s disease","authors":"Jon Esandi ,&nbsp;Pedro Renault ,&nbsp;Maria Dolores Capilla-López ,&nbsp;Rebeca Blanch ,&nbsp;Ángel Edo ,&nbsp;David Ramirez-Gómez ,&nbsp;Assumpció Bosch ,&nbsp;Beatriz Almolda ,&nbsp;Carlos Alberto Saura ,&nbsp;Jesús Giraldo ,&nbsp;Miguel Chillón","doi":"10.1016/j.biopha.2025.117815","DOIUrl":"10.1016/j.biopha.2025.117815","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-β and Tau protein depositions, with treatments focusing on single proteins have shown limited success due to the complexity of pathways involved. This study explored the potential of chronokines —proteins that modulate aging-related processes— as an alternative therapeutic approach. Specifically, we focused on a novel pleiotropic chimeric protein named HEBE, combining s-KL, sTREM2 and TIMP2, guided by bioinformatic analyses to ensure the preservation of each protein’s conformation, crucial for their functions. <em>In vitro</em> studies confirmed HEBE’s stability and enzymatic activities, even suggesting it has different activities compared to the individual chronokines. <em>In vivo</em> experiments on APP/Tau mice revealed improved learning and memory functions with HEBE treatment, along with decreased levels of phosphorylated Tau and minor effects on amyloid-β levels. These findings suggest that HEBE is as a promising therapeutic candidate for ameliorating memory deficits and reducing pTau in an AD mouse model.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117815"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in lacrimal gland organoid development: Techniques and therapeutic applications","authors":"Ahmed Abdal Dayem ,&nbsp;Soo Bin Jang ,&nbsp;Nahee Lim ,&nbsp;Han Cheol Yeo ,&nbsp;Yeonjoo Kwak ,&nbsp;Shin-Hyo Lee ,&nbsp;Hyun Jin Shin ,&nbsp;Sang-Goo Cho","doi":"10.1016/j.biopha.2025.117870","DOIUrl":"10.1016/j.biopha.2025.117870","url":null,"abstract":"<div><div>The human lacrimal gland (LG), located above the outer orbital region within the frontal bone socket, is essential in maintaining eye surface health and lubrication. It is firmly anchored to the orbital periosteum by the connective tissue, and it is vital for protecting and lubricating the eye by secreting lacrimal fluid. Disruption in the production, composition, or secretion of lacrimal fluid can lead to dry eye syndrome, a condition characterized by ocular discomfort and potential eye surface damage. This review explores the recent advancements in LG organoid generation using tissues and stem cells, highlighting cutting-edge techniques in biomaterial-based and scaffold-free technologies. Additionally, we shed light on the complex pathophysiology of LG dysfunction, providing insights into the LG physiological roles while identifying strategies for generating LG organoids and exploring their potential clinical applications. Alterations in LG morphology or secretory function can affect the tear film stability and quality, leading to various ocular pathological conditions. This comprehensive review underlines the critical crosslink of LG organoid development with disease modeling and drug screening, underscoring their potential for advancing therapeutic applications.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117870"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial efficacy of alternative root canal disinfection strategies: An evaluation on multiple working models","authors":"Victor Feliz Pedrinha ,&nbsp;Mirela Cesar Barros ,&nbsp;Juan Domingos Portes ,&nbsp;Anje Margje Slomp ,&nbsp;Willem Woudstra ,&nbsp;Osmar Alves Lameira ,&nbsp;Carmen Lucia Queiroga ,&nbsp;Maria Cristina Marcucci ,&nbsp;Mohammad-Ali Shahbazi ,&nbsp;Prashant Kumar Sharma ,&nbsp;Flaviana Bombarda de Andrade","doi":"10.1016/j.biopha.2025.117833","DOIUrl":"10.1016/j.biopha.2025.117833","url":null,"abstract":"<div><div>Researching disinfection strategies is pivotal because effectively eliminating bacteria and their byproducts during root canal treatment (RCT) remains a challenge. This study investigated the antimicrobial efficacy of natural antimicrobial compounds, propolis (PRO) and copaiba oil-resin (COR), compared to conventional agents in Endodontics. Antimicrobials were tested against endodontic pathogens via macrodilution with standardized inoculums to determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Biofilm killing efficacy were performed using two dual-species biofilms: <em>Enterococcus faecalis</em> (ATCC 29212) and <em>Streptococcus mutans</em> (ATCC 20523) and <em>Streptococcus oralis</em> (J22) and <em>Actinomyces naeslundii</em> (T14V-J1) grown on dentine discs. At the intratubular level (dentine cylinders), dentine tubule contamination was performed with <em>E. faecalis</em> and <em>S. mutans</em>. The specimens were exposed to antimicrobials to simulate their use at different sets of RCT and bacterial viability was quantified using Live/Dead staining via confocal laser scanning microscopy (CLSM). Biofilm characteristics and immediate removal of <em>S. oralis</em> and <em>A. naeslundii</em> biofilm model were evaluated employing optical coherence tomography (OCT) and CFU/mL counting. Statistical tests were applied according to data distribution for each analysis (<em>α</em>=0.05). Macrodilutions showed different effects against endodontic pathogens. Direct contact and intratubular analysis showed that PRO and COR promoted disinfection like conventional agents (<em>p</em> &gt; 0.05). According to OCT analysis, PRO and COR showed similar biofilm reduction after immediate contact (<em>p</em> &lt; 0.05). CFU/mL counting showed decontamination (<em>p</em> &lt; 0.05) after using natural and conventional agents. PRO and COR showed antimicrobial effects, indicating their suitability as complementary approaches in RCT to eliminate as much microbial load as possible.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117833"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celastrol has beneficial effects on pulmonary hypertension associated with bronchopulmonary dysplasia: Preclinical study outcomes","authors":"Claire-Marie Pilard ,&nbsp;Guillaume Cardouat ,&nbsp;Isabel Gauthereau ,&nbsp;Laure Gassiat ,&nbsp;Mathilde Dubois ,&nbsp;Paul Robillard ,&nbsp;Fanny Sauvestre ,&nbsp;Fanny Pelluard ,&nbsp;Sophie Berenguer ,&nbsp;Melie Sarreau ,&nbsp;Stéphane Claverol ,&nbsp;Caroline Tokarski ,&nbsp;Loïc Sentilhes ,&nbsp;Frederic Coatleven ,&nbsp;Marie Vincienne ,&nbsp;Roger Marthan ,&nbsp;Eric Dumas-de-la-roque ,&nbsp;Patrick Berger ,&nbsp;Mark K. Friedberg ,&nbsp;Laurent Renesme ,&nbsp;Christelle Guibert","doi":"10.1016/j.biopha.2025.117881","DOIUrl":"10.1016/j.biopha.2025.117881","url":null,"abstract":"<div><div>Pulmonary hypertension associated with bronchopulmonary dysplasia (BPD-PH) is a severe cardiorespiratory disease of preterm newborns leading to an excess of mortality in infancy and no curative treatment currently exists. Inflammation and oxidative stress are the common pathways that lead to BPD-PH. Therefore, we aimed to evaluate celastrol, a molecule with anti-inflammatory and antioxidant properties, as a promising preventive treatment in BPD-PH. In a model of neonatal rats exposed to hyperoxia, we demonstrated that mortality was prevented in animals treated with celastrol. Moreover, <em>in vivo</em>, celastrol decreased pulmonary hypertension, right ventricular hypertrophy, vascular remodeling, pulmonary arterial hyperreactivity to endothelin-1 and inflammation but had no effect on hypoalveolarization and altered angiogenesis. <em>In vitro</em> experiments carried out on human fetal pulmonary artery smooth muscle cells (HfPA-SMC) exposed to hyperoxia showed that endothelin-1-induced intracellular calcium response was increased and celastrol significantly inhibited this effect, without modifying endothelin-1 receptors expression. Regarding inflammation, celastrol decreased both CD68 staining in lung and secretion of the pro-inflammatory cytokine Tissue Inhibitor of Metalloproteinases-1 in intrapulmonary arteries from neonatal rats. IL-6 secretion was also decreased by celastrol in HfPA-SMC. Finally, hyperoxia increased heme oxygenase-1 (HO-1) expression and celastrol induced an overexpression of HO-1 in both neonatal rat lung and human cells. These results suggest that celastrol has a preventive effect on major hallmarks of PH in both a rat hyperoxic model of BPD-PH and HfPA-SMC exposed to hyperoxia via modulation of macrophage inflammatory signaling and HfPA-SMC calcium cycling. Celastrol could therefore be considered as a promising preventive treatment in BPD-PH.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117881"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex gene-dependent and-independent mechanisms control daily rhythms of hematopoietic cells","authors":"Francesca Sciarra,&nbsp;Edoardo Franceschini,&nbsp;Gabriella Palmieri,&nbsp;Mary Anna Venneri","doi":"10.1016/j.biopha.2024.117803","DOIUrl":"10.1016/j.biopha.2024.117803","url":null,"abstract":"<div><div>The abundance and behaviour of all hematopoietic components display daily oscillations, supporting the involvement of circadian clock mechanisms. The daily variations of immune cell functions, such as trafficking between blood and tissues, differentiation, proliferation, and effector capabilities are regulated by complex intrinsic (cell-based) and extrinsic (neuro-hormonal, organism-based) mechanisms. While the role of the transcriptional/translational molecular machinery, driven by a set of well-conserved genes (Clock genes), in nucleated immune cells is increasingly recognized and understood, the presence of non-transcriptional mechanisms remains almost entirely unexplored. Studies on anucleate hematopoietic components, such as red blood cells and platelets, have shown that auto-sustained redox reaction cycles persist and operate in mammals. This opens to the possibility that transcriptional and non-transcriptional circadian mechanisms might coexist in nucleated immune cell populations, potentially complementing each other.</div><div>It is becoming increasingly clear that disruption of the circadian rhythm at the central level (core clock) is strongly implicated in a plethora of diseases that are associated with maladaptive immune responses. On the other hand, several evidence imply that dysregulated immune activity (e.g. excessive inflammation) may alter/disrupt the proper functioning of peripheral clocks. This knowledge paves the way to the exploitation of chronobiological concepts in clinical practice. A better comprehension of various transcriptional/translational and biochemical mechanisms that maintain rhythmicity in immune system activities, as well as the many factors (host-derived, microbiota-derived, environment) that can alter or disrupt these processes, will facilitate the development of novel chrono-immunotherapeutic approaches.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117803"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cationic and anionic PLGA-cholesterol hybrid nanoparticles as promising platforms to enhance the trypanocidal efficacy of benznidazole and drug delivery in Trypanosoma cruzi-infected cells","authors":"Thayse Silva Medeiros ,&nbsp;Lucas Eduardo Bezerra de Lima ,&nbsp;Eron Lincoln Alves-Pereira ,&nbsp;Mariana Farias Alves-Silva ,&nbsp;Douglas Dourado ,&nbsp;Matheus de Freitas Fernandes-Pedrosa ,&nbsp;Regina Celia Bressan Queiroz de Figueiredo ,&nbsp;Arnóbio Antônio da Silva-Junior","doi":"10.1016/j.biopha.2024.117782","DOIUrl":"10.1016/j.biopha.2024.117782","url":null,"abstract":"<div><div>Chagas disease is a neglected tropical disease caused by the protozoan <em>Trypanosoma cruzi</em>, remains a significant global health challenge. Currently, benznidazole (BNZ) is the primary treatment in many countries. However, this drug is limited by low bioavailability, significant host toxicity, and reduced efficacy in chronic disease phase. Additionally, cases of parasite resistance to treatment and low efficacy in in chronic disease phase have been reported. In this context, nanotechnology formulations for intracellular drug delivery have emerged as a promising alternative to improve the pharmacological properties of BNZ. In this study, we developed and evaluated cationic and anionic PLGA-cholesterol hybrid nanoparticles (HNPs) as innovative drug delivery systems for BNZ. These HNPs, functionalized with polyethyleneimine, were synthesized using a composition-dependent self-assembly method, yielding stable nanosystems with tuneable physicochemical properties. Furthermore, four release kinetic models were applied and Peppas-Sahlin demonstrated the best fit. In vitro assays confirmed the biocompatibility of HNPs with cardiomyoblasts at tested concentrations and revealed significantly enhanced trypanocidal activity against intracellular amastigotes compared to free BNZ. Transmission electron microscopy and fluorescence microscopy analyses highlighted effective nanoparticle internalization, with superior performance trypanocidal observed in anionic HNPs, which can be attributed to the residence of cationic in endo/lysosomal vesicles. Taken together, our results demonstrate the successful development of HNPs, underscoring their potential as a promising platform for the intracellular delivery of therapeutic agents.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117782"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}