Current pharmaceutical design最新文献

{"title":"Beyond the Barrier: Orchestrating Precision Dermatology Through Personalized Dermal Drug Delivery.","authors":"Aditya Dev Rajora, Praveen Halagali, Amrita Roy, Farhath Sherin, Moumita Saha, Srinivas Mutalik, Sudheer Moorkoth, Vamshi Krishna Tippavajhala, Ashutosh Gupta, Soji Soman","doi":"10.2174/0113816128484150260719144129","DOIUrl":"https://doi.org/10.2174/0113816128484150260719144129","url":null,"abstract":"<p><p>Dermatoses comprise a diverse group of skin disorders that compromise skin integrity, adversely affect patient health, and significantly reduce quality of life. These conditions are often associated with inflammation, infection, and disease progression, necessitating personalized therapeutic strategies and long-term management. Recent advances in molecular biology have facilitated the identification of biomarkers associated with disease onset, progression, and treatment response. These biomarkers provide valuable insights into disease pathophysiology and support early diagnosis, prognosis, and therapeutic monitoring. This review presents a comprehensive overview of gene expression profiles and biomarkers associated with various dermatological disorders. Understanding biomarker signatures enables the development of targeted and personalized therapeutic approaches tailored to individual patients, thereby improving treatment efficacy and clinical outcomes. In addition, this review highlights the role of nanocarrier-based systems in dermal drug delivery. Compared with conventional formulations, nanoparticle-based nanocarriers improve drug stability, enhance bioavailability, enable controlled drug release, minimize systemic toxicity, and reduce off-target drug delivery, making them promising platforms for the effective management of dermatological disorders.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imatinib: A Multifunctional Tyrosine Kinase Inhibitor with Diverse Mechanisms Targeting BCR-ABL, c-KIT, and PDGFR in Cancer Therapy.","authors":"Dilpreet Singh, Sanchit Dhankhar, Karan Goel, Samrat Chauhan, Sumesh Chandra Sharma, Monika Saini, Thakur Gurjeet Singh, Somdutt Mujwar","doi":"10.2174/0113816128488564260713055506","DOIUrl":"https://doi.org/10.2174/0113816128488564260713055506","url":null,"abstract":"<p><p>Imatinib, a Tyrosine Kinase Inhibitor (TKI) that targets the first-in-class, has been a major factor in the change of cancer treatment aimed at precision by selectively blocking Breakpoint Cluster Region-Abelson murine leukemia viral oncogene (BCR-ABL), KIT proto-oncogene receptor tyrosine kinase (c-KIT), and platelet-Derived Growth Factor Receptors (PDGFRs), along with additional inhibitory activity against Src Family Kinases (SFKs). Apart from Chronic Myeloid Leukemia (CML), for which it was first approved, clinicians have now expanded its application to include Gastrointestinal Stromal Tumors (GIST), Dermatofibrosarcoma Protuberans (DFSP), and kinase-driven cancers of various types. Imatinib inhibits phosphorylation and activation of cancer pathways by competitively binding to the ATP-binding site on these kinases. Inhibiting BCR-ABL thus deprives the leukemic cells of growth and survival signals. In the same way, inhibition of c-KIT and PDGFR results in GIST and DFSP tumor growth retardation through the impact on signaling pathways like PI3K/AKT (cell survival and proliferation), RAS/MAPK (tumor growth and differentiation), and JAK/STAT (immune evasion and cytokine signaling). Moreover, imatinib exerts anti-angiogenic properties by lowering the production of pro-angiogenic factors, hence preventing tumor vascularization. However, the drawback of imatinib in the form of resistance issues still hampers the progress of the dominant division. The causes of this phenomenon are secondary mutations, alterations of the kinase domain, activation of alternative pathways, and clonal evolution. This explores imatinib's inner mechanism in detail, the pivotal role it plays in modulating tumor/stromal cell interactions, as well as the impact that resistance mechanisms have on the therapy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive Nutraceuticals in Diabetic Neuropathy: Mechanistic Insights and Gaps in Clinical Translation.","authors":"Manish Kumar Gautam, Sandip Mondal, Arup Dey, Amit Lather, Tanuj Hooda","doi":"10.2174/0113816128459735260702161801","DOIUrl":"https://doi.org/10.2174/0113816128459735260702161801","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic neuropathy (DN) serves as a widespread and incapacitating complication that affects almost fifty percent of diabetes mellitus patients while causing severe chronic pain and sensory impairment and raising the chances of limb amputation. The disease develops through multiple interconnected pathways that start with polyol pathway hyperactivity, lead to RAGE signalling by advanced glycation endproducts, and then to oxidative stress, nitrosative stress, chronic inflammation, and, finally, mitochondrial dysfunction. Existing drug treatments only address symptoms of medical conditions, yet they yield minimal benefit while causing harmful side effects, underscoring the need for treatments that target specific disease mechanisms. This review aims to provide a mechanistically oriented evaluation of bioactive nutraceuticals and their potential role in modulating key pathogenic pathways driving diabetic nephropathy, while also identifying essential research requirements for clinical application.</p><p><strong>Methods: </strong>The researchers conducted a narrative synthesis of existing studies examining the primary categories of bioactive nutraceuticals, including polyphenols and flavonoids, phenolic acids, organosulfur compounds, isothiocyanates, and terpenoids. The research focused on how these substances affected the biological processes that generate oxidative stress and inflammation, leading to mitochondrial dysfunction and metabolic disorders.</p><p><strong>Results: </strong>Preclinical evidence suggests that various nutraceutical compounds, including epigallocatechin gallate, resveratrol, curcumin, chlorogenic acid, S-allyl cysteine, sulforaphane, and cinnamaldehyde, demonstrate neuroprotective effects by controlling different disease-related mechanisms. The compounds show the ability to decrease oxidative stress while also blocking inflammatory pathways and enhancing mitochondrial performance, and they help to restore metabolic equilibrium. The existing evidence mainly comes from laboratory and animal research, as few high-quality clinical studies specifically examine human outcomes in neuropathic conditions. The field faces major obstacles due to low bioavailability, unstandardized extract products, inconsistent dosing methods, and insufficient understanding of pharmacokinetic properties.</p><p><strong>Conclusion: </strong>Bioactive nutraceuticals serve as a multi-target therapeutic approach with potential for treating diabetic neuropathy. Yet their translation into clinical use faces major obstacles that restrict their application. The research work should focus on developing standard product formulas together with advanced delivery methods and comprehensive clinical studies, which will demonstrate product effectiveness, safety, and medical value in human subjects.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data Collection and Management for AI-Based Pharmaceutical Formulation Development: A Comprehensive Review.","authors":"Pritam Kayal, Priyam Manna, Ramit Rahaman, Mohan Kumar Ramar, Abimanyu Sugumaran, Natarajan Jawahar","doi":"10.2174/0113816128448261260727113834","DOIUrl":"https://doi.org/10.2174/0113816128448261260727113834","url":null,"abstract":"<p><strong>Introduction: </strong>Traditional pharmacovigilance relies on slow clinical trials and post-marketing studies with limited coverage. This review synthesizes evidence on Real-World Data (RWD) integration with Artificial Intelligence (AI) for enhanced Adverse Drug Reaction (ADR) detection, evaluates generative AI like ChatGPT-4 and LLaMA-2 in Substance Use Disorder (SUD) scenarios, discusses current applications, and outlines future directions. The objective is to guide researchers, clinicians, and regulators in this evolving field.</p><p><strong>Methods: </strong>Literature was reviewed on RWD sources (EHRs, claims, registries, wearables), AI algorithms (supervised/ unsupervised learning, NLP, deep learning), and regulatory frameworks. Generative AI performance was assessed via clinician-blind evaluation of responses to Reddit-sourced SUD queries from r/stopdrinking, r/leaves, and r/OpiatesRecovery, with fact-checking against SAMHSA/FDA guidelines and consistency testing. Data included tables comparing RWD, algorithms, and AI models.</p><p><strong>Results: </strong>AI enables real-time ADR signals via RWD-AI in CCM, improving diagnostics, personalization, and drug discovery. ChatGPT-4 suggested unsafe opioid microdosing; LLaMA-2 referenced nonexistent resources and improper Xanax sharing, both showing severe inaccuracies in SUD contexts. Tables highlight RWD applications, algorithm uses, and AI limitations like bias and inconsistency.</p><p><strong>Discussion: </strong>RWD-AI transforms pharmacovigilance but faces bias, transparency, and validation challenges. FHIR/DLT enhance secure exchange; generative AIs require oversight. Implications include equitable safety monitoring via bias mitigation and regulatory compliance.</p><p><strong>Conclusion: </strong>AI-RWD integration advances ADR detection and personalized safety, despite generative AI risks in SUD management. Future success demands validated LLMs, FHIR/blockchain infrastructure, and clinician collaboration for comprehensive, equitable pharmacovigilance.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical Profiling, Anti-Tick and Antimicrobial Activities of Cedrus deodara (Roxb.) G. Don Oil Extracted Using Traditional Chula and Hydrodistillation Methods.","authors":"Ram Prasad Baral, Kusum Shrestha, Rameshwar Adhikari, Prabodh Satyal, Achyut Adhikari","doi":"10.2174/0113816128406780260727064356","DOIUrl":"https://doi.org/10.2174/0113816128406780260727064356","url":null,"abstract":"<p><strong>Introduction: </strong>Bio-insecticides are becoming increasingly important due to the toxicity of many synthetic insecticides. The tar (Diyar oil) of the plant Cedrus deodara, extracted by the traditional Chula method, is used by local people in Karnali, Nepal, to repel ticks and fleas on cattle. This study aims to perform chemical profiling and assess the anti-tick potential of Cedrus deodara.</p><p><strong>Methods: </strong>The tar, which is also called Diyar Oil (DO), was extracted using the traditional Chula method, and the Essential Oil (EO) of Cedrus deodara was obtained by hydrodistillation. Gas chromatography-mass spectrometry (GC-MS) was used to identify the chemical compounds in DO and EO. The anti-tick, antimicrobial, and antioxidant activities were performed using the contact method, agar-well diffusion method, and DPPH assay.</p><p><strong>Results: </strong>The GC-MS analysis showed the presence of atlantone (25.81%) and β-himachalene (12.06%) in Deodara Oil (DO), and the Essential Oil was dominated by β-himachalene (21.95%) and trans-, α-atlantone (15.02%). DO (2500 ppm) and EO (2500 ppm) eradicated full ticks by 4 h, outperforming the standard drug Flumethrin. Both DO and EO were found to be effective against Escherichia coli. Both DO and EO were found to be DPPH radical scavengers with IC50 values of 0.248 ± 0.0042 μg/mL for DO and 0.148 ± 0.0042 μg/mL, respectively.</p><p><strong>Discussion: </strong>Both DO and EO at 2500 ppm show potent anti-tick activity, and atlatone and β-himachalene are the major compounds in both DO and EO.</p><p><strong>Conclusion: </strong>The oil of Cedrus deodara may be a potential natural anti-tick agent.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ostreae Concha Extract Mitigates Sleep Disturbances Through 5-HT and Vagus Nerve-Mediated Gut-Brain Axis Pathways.","authors":"Feng Lu, Qinyu Wang, Qian Wang, Xun Ye, Zibo Liu, Chunjie Wu","doi":"10.2174/0113816128487198260714205131","DOIUrl":"https://doi.org/10.2174/0113816128487198260714205131","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigates the mechanism by which Ostreae Concha (OC), a traditional Chinese medicinal material derived from oyster shells, alleviates insomnia.</p><p><strong>Methods: </strong>A chronic insomnia mouse model was established and assessed using behavioral tests, Nissl staining, biochemical assays, immunofluorescence, and ELISA.</p><p><strong>Results: </strong>The aqueous extract of OC improved locomotion and anxiety-like behaviors, increased hippocampal Nissl bodies, reduced brain malondialdehyde (MDA) levels, lowered plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT), and elevated 5-hydroxytryptamine (5-HT) and c-Fos expression in the nucleus of the solitary tract. In vitro experiments demonstrated that the inorganic components of OC enhanced the expression of proteins related to 5-HT synthesis, independently of calcium channels. Based on these findings, we propose that OC may form calcium carbonate nanoparticles in vivo, which stimulate intestinal chromaffin cells to release 5-HT. This signal is then transmitted via the vagus nerve to suppress overactivation of the hypothalamic-pituitary-adrenal (HPA) axis, thereby producing sedative and calming effects.</p><p><strong>Discussion: </strong>The findings confirm OC's sedative and hypnotic effects by regulating the 5-HT system and HPA axis, consistent with its traditional application in treating insomnia. The inorganic components' role in 5-HT synthesis, independent of calcium channels, reveals a novel mechanism of OC. Additionally, OC's derivation from aquaculture waste highlights its potential in resource recycling, offering a basis for further development of OC-based sleep-improving products and ecological resource utilization.</p><p><strong>Conclusion: </strong>This work not only provides experimental evidence for the use of OC in sleep improvement but also suggests a potential pathway for the sustainable, high-value utilization of aquaculture waste, aligning ecological conservation with resource sustainability.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoprotective Effects of Nigella sativa and Thymoquinone: Modulation of CYP450 Enzymes and Cytochrome c Reductase in CCl4-Induced Hepatotoxicity.","authors":"Mohammed A Abdel-Rasol, Alyaa S Abdel Halim, Rasha A Hussein, Wael M El-Sayed","doi":"10.2174/0113816128422260251127064603","DOIUrl":"https://doi.org/10.2174/0113816128422260251127064603","url":null,"abstract":"<p><strong>Introduction: </strong>Carbon tetrachloride (CCl4) is a potent hepatotoxin that disrupts mitochondrial function and alters cytochrome P450 (CYP450) enzyme activity. Nigella sativa (Ns) and its primary bioactive compound, thymoquinone (TQ), are known for their hepatoprotective properties, but their effects on CYP450 modulation in liver injury remain underexplored. This study aimed to evaluate the effects of Ns and TQ on CYP450 activity and expression in CCl4-induced liver injury.</p><p><strong>Methods: </strong>Forty-two male albino rats were divided into six groups: control, Ns-treated (50 mg/kg), TQ-treated (5 mg/kg), CCl4-exposed (1 mL/kg, single i.p. injection), and two combination groups pretreated with Ns or TQ followed by CCl4 administration. Ns and TQ were administered orally for five days, with CCl4 given on day three. Serum ALT, total CYP450 content, cytochrome c reductase activity, and specific CYP isoform activities and expression were measured. Statistical significance was set at p < 0.05 using one-way ANOVA with Tukey's post hoc test.</p><p><strong>Results: </strong>CCl4 exposure significantly elevated ALT levels, decreased total CYP450 activity by 61%, and reduced cytochrome c reductase activity by 50%. It suppressed the activities of CYP3A1, CYP2C9, and CYP2D6 while upregulating CYP1B1 and CYP2E1. Ns and TQ pretreatment attenuated these effects by reducing ALT levels, restoring cytochrome c reductase activity, and partially normalizing CYP3A1 and CYP2D6 activities. Ns produced stronger hepatoprotective effects than TQ.</p><p><strong>Discussion: </strong>The observed effects indicate that CCl4-induced liver injury is accompanied by broad CYP450 dysregulation, and that Ns and TQ provide significant protection by restoring enzymatic balance and mitochondrial function.</p><p><strong>Conclusion: </strong>Ns and TQ mitigate CCl₄-induced hepatotoxicity through modulation of CYP450 enzymes and improvement of mitochondrial function, suggesting their potential therapeutic use in oxidative stress-related liver dysfunction.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Antibacterial Mechanisms of Bletilla striata: A Synergistic Approach Combining Network Pharmacology, Molecular Docking, and In Vitro Validation.","authors":"Zitai Sang, Yin Meng, Yuxuan Wang, Yaojia Zhang, Mengfan He, Xixi Zhou, Ruonan Wang","doi":"10.2174/0113816128477312260721062613","DOIUrl":"https://doi.org/10.2174/0113816128477312260721062613","url":null,"abstract":"<p><strong>Introduction: </strong>Bletilla striata, a traditional Chinese medicinal herb, shows promise for treating bacterial infections, but its precise antibacterial mechanisms are not fully understood.</p><p><strong>Materials and methods: </strong>An integrated strategy was employed. Network pharmacology identified bioactive compounds from Bletilla striata and predicted antibacterial targets. Molecular docking assessed interactions between key compounds and core targets (ESR1, EGFR, PTGS2, MAPK14), followed by molecular dynamics simulations for the top complex (BJ6-ESR1). In vitro assays evaluated the antibacterial activity, anti-persister effects, and potential for resistance induction of the key compound BJ6 against S. aureus and Gram-negative bacteria.</p><p><strong>Results: </strong>Nine bioactive compounds were identified. 4,7-dihydroxy-1-p-hydroxybenzyl-2-methoxy-9,10- dihydrophenanthrene (BJ6) showed the strongest binding to key targets in docking. MD simulations confirmed a stable BJ6-ESR1 complex with a high binding free energy of -39.98 kcal/mol. In vitro, BJ6 exhibited potent activity against S. aureus (MIC = 1~2 μg/mL), significant efficacy against persister cells, and a delayed development of bacterial resistance compared to amoxicillin.</p><p><strong>Discussion: </strong>The findings indicate that Bletilla striata, primarily through BJ6, exerts antibacterial effects via multi-component, multi-target interactions, particularly with ESR1, EGFR, PTGS2, and MAPK14.</p><p><strong>Conclusion: </strong>This study elucidates the molecular basis of Bletilla striata's antibacterial activity, highlighting BJ6 as a key bioactive component.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modern Trends in the Development of Natural and Synthetic Anti-Tuberculosis Drugs.","authors":"David Calderon Guzman, Hugo Juarez Olguin, Francisca Trujillo Jimenez, Ernestina Hernandez Garcia, Maribel Ortiz Herrera, Alberto Rojas Ochoa, Daniel Santamaria Del Angel, Juan Luis Chavez Pacheco","doi":"10.2174/0113816128487631260714165258","DOIUrl":"https://doi.org/10.2174/0113816128487631260714165258","url":null,"abstract":"<p><p>Tuberculosis (TB) pathogenesis is driven by the rapid proliferation of Mycobacterium tuberculosis bacilli, which breach host defenses to invade pulmonary tissue and precipitate active disease. While both natural and synthetic compounds have contributed to successful Mycobacterium tuberculosis (Mtb) therapies, researchers should now prioritize harnessing the synergistic effects of complementary treatments to maximize efficacy. Deploying natural and synthetic small molecules offers a powerful strategy to circumvent drug resistance, enhance Mycobacterium tuberculosis (MTB) therapeutic efficacy, and minimize the toxicities associated with conventional regimens and emerging PROTAC modalities. Consequently, clarifying how these natural and synthetic agents target resistant strains and alter associated genetic biomarkers is essential. This paper reviews recent advancements in natural and synthetic drugs, highlighting their structure-activity relationships to enhance anti-tuberculosis (TB) therapies. Additionally, we present a novel computational framework utilizing target prediction and probability scoring to identify high-potential synthetic compounds for future first-line TB regimens.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation, Characterization, and Preliminary In Vitro Evaluation of Letrozole Incorporated Eudragit® RS 100 Nanoparticles Using HepG2 Cells.","authors":"Muhammet Ali Polat, Kadir Aykaç, Zerrin Cantürk, Ebru Başaran","doi":"10.2174/0113816128474280260720051151","DOIUrl":"https://doi.org/10.2174/0113816128474280260720051151","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Letrozole (LTZ)-loaded polymeric nanoparticles (PNPs) were formulated with Eudragit® RS100 to investigate their potential as a preliminary drug delivery system for hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>Nanoparticles were prepared using the spray-drying technique with a Büchi B-90 Nano Spray Dryer and characterized in terms of morphology, particle size, polydispersity index (PDI), zeta potential, drug loading efficiency, thermal and structural characteristics, in vitro release behavior, and preliminary cytotoxicity.</p><p><strong>Results: </strong>SEM analysis demonstrated the formation of predominantly spherical particles with relatively smooth surfaces. The prepared nanoparticles exhibited initial particle sizes ranging between 253 nm and 425 nm, with PDI values of 0.3-0.4 and positive zeta potential values between 36 and 48 mV. Encapsulation efficiency (EE%) and drug loading (DL%) values were determined as 47.9%-56.9% and 9.1%-18.6%, respectively. Thermal and structural analyses indicated the molecular dispersion of LTZ within the polymeric matrix. In vitro release studies conducted at pH 7.4 demonstrated an initial burst release, followed by a sustained drug release profile over 24 h, with cumulative drug release reaching almost 80%. The preliminary cytotoxicity of the formulations was evaluated using the methylthiazolyl-diphenyl-tetrazolium bromide (MTT) assay on human hepatocellular carcinoma (HepG2) and healthy human dermal fibroblast (BJ) cell lines. Free LTZ demonstrated an IC50 value of 142.76 µg/mL against HepG2 cells, whereas the optimized nanoparticle formulation exhibited an IC50 value higher than 121.85 µg/mL.</p><p><strong>Discussion: </strong>The obtained results confirmed the successful development of LTZ-loaded polymeric nanoparticles with suitable physicochemical properties, efficient drug encapsulation, and sustained release behavior. The positive surface charge and nanoscale size may support formulation stability. Furthermore, the nanoparticles preserved the cytotoxic activity of LTZ, indicating their potential as an effective drug delivery system.</p><p><strong>Conclusion: </strong>Overall, the findings suggest that the developed nanoparticles constitute a promising drug delivery system for further investigation in HCC-related therapy. However, additional mechanistic studies and in vivo evaluations are required to comprehensively assess their true therapeutic potential.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}