Drug Development Research最新文献

{"title":"Inhibition of Steroidogenesis in Prostate Cancer Cells by Both a Natural and Another Synthetic Steroid","authors":"Marisa Cabeza,&nbsp;Karla Mejía,&nbsp;Fernando García,&nbsp;Ivonne Heuze,&nbsp;Miguel Morales,&nbsp;Mauricio Rodríguez-Dorantes","doi":"10.1002/ddr.70078","DOIUrl":"https://doi.org/10.1002/ddr.70078","url":null,"abstract":"<p>Studies suggest that vegetarians and Asians have lower mortality rates from prostate cancer compared to men who follow a Western diet. β-sitosterol, a key compound of plant-based diets, has been found to induce significant changes in the ultrasonic structure of the prostatic adenomas, making it a promising candidate for further prostate cancer research. Consequently, we investigated the potential of β-sitosterol and the synthetic derivative <b>2</b> as potent inhibitors of androgen synthesis, a critical process for the growth and survival of prostate tumor LNCaP cells. Solubilized LNCaP microsomes were used as a source of SRD5A1 and AKR1C3 to monitor androgen synthesis from labeled androstenedione, both in the presence and absence of β-sitosterol or <b>2</b>. Furthermore, the effect of these steroids on LNCaP viability was determined using the MTT method. Our findings revealed significant insights into the androgen synthesis pathways in LNCaP cells. The most efficient metabolic route for dihydrotestosterone formation was the conversion of androstenedione to 5α-androstanedione rather than from testosterone in LNCaP. This conclusion is supported by the Vmax values for 5α-androstanedione formation (271.05 ± 5.0 ng/mg protein/min) and the Vmax of testosterone formation (80.1 ± 8.0 ng/mg protein/min). Both β-sitosterol and <b>2</b> demonstrated substantial inhibitory effects of these enzymes for dihydrotestosterone formation and significantly reduced cell viability, highlighting their therapeutic potential. These findings enhance our understanding of the inhibitory effects of β-sitosterol and <b>2</b> on LNCaP cells and suggest their promising application in the treatment of prostate cancer.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689922","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}

{"title":"Design, Synthesis and Anti-Influenza Virus Activity of 4-Tert-Butyl-N-(3-Oxo-1-Thia-4-Azaspiro[4.5]Dec-4-yl)Benzamide Derivatives That Target Hemagglutinin-Mediated Fusion","authors":"Gözde Çınar,&nbsp;Zeynep Alikadıoğlu,&nbsp;Özge Soylu-Eter,&nbsp;Lieve Naesens,&nbsp;Gökçe Cihan-Üstündağ","doi":"10.1002/ddr.70080","DOIUrl":"https://doi.org/10.1002/ddr.70080","url":null,"abstract":"<p>Hemagglutinin (HA) is a viral glycoprotein that mediates influenza virus entry into the host cell and is considered a relevant viral target. We here report the identification of a class of 4-<i>tert</i>-butylphenyl-substituted spirothiazolidinones as HA-mediated fusion inhibitors with specific activity against influenza A/H3N2 virus. The novel spirocyclic compounds were achieved by using one-pot cyclocondensation method and the chemical structures were characterized by IR, ¹H NMR, ¹³C NMR, and elemental analysis. Compound <b>2c</b>, bearing methyl substitutions at positions 2- and 8- of the spiro ring displayed an EC₅₀ value against influenza A/H3N2 virus of 1.3 μM and an antiviral selectivity index of 30. The fusion-inhibiting effect of compound <b>2c</b> was revealed in the polykaryon assay which is based on cell-cell fusion when influenza virus H3 HA-transfected cells are exposed to low pH. Computer-aided docking was performed to predict the possible binding pocket in the H3 HA trimer. Resistance data and <i>in silico</i> studies indicated that compound <b>2c</b> has an overlapping binding pocket in the stem region of H3 HA with the known fusion inhibitors TBHQ and arbidol.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689447","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}

{"title":"Novel Benzosuberone/Indanone-Linked Thiazoles as Small-Molecule SARS-CoV-2 Main Protease Inhibitors","authors":"Thoraya A. Farghaly,&nbsp;Elham N. Bifari,&nbsp;Mariam A. Al-sheikh,&nbsp;Afaf Y. Khormi,&nbsp;Hanadi Y. Medrasi,&nbsp;Jihan Qurban,&nbsp;Hanan Gaber Abdulwahab","doi":"10.1002/ddr.70081","DOIUrl":"10.1002/ddr.70081","url":null,"abstract":"<div>\u0000 \u0000 <p>Herein, novel benzosuberone/indanone-linked thiazoles were designed and synthesized as small-molecule SARS-CoV-2 Main protease (M^pro) inhibitors with potential anti-COVID activity. All thiazole derivatives were synthesized from the reaction of thiosemicarbazone derivatives with α-halocarbonyl derivatives. The structures of novel benzosuberone/indanone-linked thiazoles were confirmed based on their spectral data. Thiazolyl-benzosuberone <b>9d</b> and thiazolyl-indanone <b>14</b> were the most potent against M^pro displaying one-digit IC₅₀ values of 5.94 and 8.47 µM, respectively, compared to ritonavir (IC₅₀ = 2.4 µM). Moreover, antiviral assay revealed the ability of compounds <b>9d</b> and <b>14</b> to inhibit the replication of SARS-CoV-2 in Vero cells at EC₅₀ values of 9.33 and 28.75 µM, respectively, relative to ritonavir (EC₅₀ = 1.72 µM). Cytotoxicity assay in Vero cells was also conducted. <b>9d</b> and <b>14</b> showed CC₅₀ values of 289.63 and 229.42 µM and SI of 31.0 and 7.9, respectively. In addition, a docking study revealed proper orientation and well-fitting of title compounds into the binding pocket of SARS-CoV-2 M^pro.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669279","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":"Panaxadiol Attenuates Brain Damage by Inhibiting Ferroptosis in a Rat Model of Cerebral Hemorrhage","authors":"Min Zhao,&nbsp;Yu Wang,&nbsp;Jing Li,&nbsp;Quan Wen,&nbsp;Yue Liu,&nbsp;Yanan Zhao","doi":"10.1002/ddr.70079","DOIUrl":"10.1002/ddr.70079","url":null,"abstract":"<div>\u0000 \u0000 <p>Intracerebral hemorrhage (ICH) is the most common subtype of hemorrhage stroke, with a high disability, morbidity and mortality rate globally. Panaxadiol (PD), a triterpenoid sapogenin monomer, is isolated from the roots of ginseng, which has shown a variety of biological properties, such as anti-inflammation, anti-cancer, and neuroprotection. However, its effect and mechanism on ICH were still unknown. Thirty-six rats were randomly divided into six group (<i>n</i> = 6), namely, sham, ICH, ICH + 5 mg/kg PD, ICH + 10 mg/kg PD, ICH + 20 mg/kg PD, and ICH + 10 mg/kg PD + 50 mg/kg vismodegib. Rats were treated with type IV collagenase to induce an in vivo model of ICH, and then intraperitoneally injected with PD (5, 10 and 20 mg/kg) and 50 mg/kg vismodegib (an inhibitor of hedgehog signal). The effect and potential mechanism of PD on ICH were explored by behavioral test, brain water content measurement, Evans blue detection, hematoxylin-eosin (HE) staining, iron level examination, Prussian blue staining, western blot and immunohistochemistry, respectively. An increase in the mNSS (13.17 ± 1.17), and a decrease in the rotarod latency (40.67 ± 9.31), modified Garcia score (9.83 ± 1.47), forelimb use times (3.33 ± 0.82), left forepaw placements (29.90 ± 4.38) and left turns (17.34 ± 3.55) in ICH rats were reversed with the PD treatment (6.83 ± 0.75, 113.5 ± 11.95, 17.50 ± 1.87, 8.17 ± 0.98, 63.56 ± 9.84, and 42.13 ± 4.52 respectively). PD treatment reduced the brain water content (73.13 ± 3.16 vs. 86.82 ± 4.74), the level of Evans blue (2.14 ± 0.25 vs. 4.03 ± 0.20) and cerebral hemorrhage in ICH rats. Also, PD injection decreased the iron level (0.06 ± 0.005 vs. 0.17 ± 0.02) and the expression of ACSL4 (0.56 ± 0.07 vs. 1.23 ± 0.16), with the increased expression of GPX4 (1.14 ± 0.08 vs. 0.21 ± 0.03) in ICH rats. Mechanically, PD treatment restored the decreased expression of SHH (0.96 ± 0.13 vs. 0.20 ± 0.03), GLI1 (0.89 ± 0.13 vs. 0.06 ± 0.007) and PTCH (0.75 ± 0.05 vs. 0.10 ± 0.01) in ICH rats. Inhibition of SHH signaling by vismodegib reversed the ameliorative effect of PD on ICH rats. PD improved brain damage by suppressing ferroptosis via the activation of the SHH/GLI signaling pathway, which could lay a theoretical foundation for the treatment of ICH.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673545","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":"A Novel Topical Compound Gel Loading Minoxidil and Tofacitinib for Treatment of Alopecia Areata: Formulation, Characterization, and In Vitro/In Vivo Evaluation","authors":"Rui Wang,&nbsp;Ying Zhou,&nbsp;Peng Yang,&nbsp;Hailong Zhang,&nbsp;Jinsong Ding","doi":"10.1002/ddr.70076","DOIUrl":"https://doi.org/10.1002/ddr.70076","url":null,"abstract":"<div>\u0000 \u0000 <p>Although topical minoxidil is the most common drug for alopecia areata (AA), it has limited therapeutic effect in the treatment of patients with moderate and severe AA because it can only promote hair follicle growth and improve the characteristics of hair follicle degeneration in AA and cannot alleviate local inflammatory response. Therefore, we designed a novel topical compound gel loading minoxidil and Janus kinases (JAK) inhibitors tofacitinib. The compound gel not only had good semi-solid properties and the effect of permeation but also maintained stability for up to 3 months under accelerated conditions, ensuring the long-term quality of the formulation. This compound gel can effectively improve hair follicle growth and significantly alleviate local inflammatory response by downregulation of the ratio of inflammatory factor interferon-γ to anti-inflammatory factor interleukin-4 in C3H/HeN mice bearing AA, achieving the purpose of synergistic treatment of AA. The first combination of minoxidil and tofacitinib in a topical formulation gives a new idea for the clinical treatment of AA.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645812","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":"Innovative Multitarget Organoselenium Hybrids With Apoptotic and Anti-Inflammatory Properties Acting as JAK1/STAT3 Suppressors","authors":"Saad Shaaban,&nbsp;Aya Yaseen Mahmood Alabdali,&nbsp;Mai H. A. Mousa,&nbsp;Hussein Ba-Ghazal,&nbsp;Yasair S. Al-Faiyz,&nbsp;Ibrahim Elghamry,&nbsp;Hanan A. Althikrallah,&nbsp;Arwa Omar Al Khatib,&nbsp;Mohamed Alaasar,&nbsp;Ahmed A. Al-Karmalawy","doi":"10.1002/ddr.70075","DOIUrl":"https://doi.org/10.1002/ddr.70075","url":null,"abstract":"<div>\u0000 \u0000 <p>Herein, we report the design, synthesis, and characterization of novel organoselenium (OSe) hybrids (<b>5</b>–<b>19</b>) via modifications of the lead, <i>N</i>-(4-selaneylphenyl)-2-selaneylacetamide. The OSe-based thiazol <b>9</b> showed the highest growth inhibition % (GI%) of 64.72% relative to the positive reference doxorubicin (DOX), with a GI% of 79.5%. Furthermore, the novel OSe derivatives showed low GI% values compared to the normal cell lines employed, demonstrating their selectivity. The OSe tethered <i>N</i>-chloroacetamide <b>5</b> and Schiff base <b>19</b> showed a cytotoxic effect with an IC₅₀ of (25.07 and 11.61 µM), respectively, against the A549 tumor cell line and IC₅₀ of (34.22 and 20.12 µM), respectively, against the HELA cancer cell line. Enzyme-linked immunosorbent assay to study the JAK1 and the STAT3 inhibitory potentials of OSe compounds <b>5</b> and <b>19</b> in the A549 cancer cells both showed promising inhibitory activities with IC₅₀ values of 25.07 and 11.61 µM, respectively. Protein expression analysis on the A549 cancer cell line on OSe compounds <b>5</b> and <b>19</b> showed upregulation of P53, BAX, and Caspases 3, 6, 8, and 9 as apoptotic proteins. However, both candidates expressed downregulation of the antiapoptotic proteins (BCL2, MMP2, and MMP9). Moreover, OSe compounds <b>5</b> and <b>19</b> described the downregulation of the examined inflammatory proteins: COX2, IL-6, and IL-1β. In addition, OSe compound <b>19</b> showed potential cell cycle arrest at the G0, S, and G2-M layers, with an increase in cellular levels. Finally, molecular docking studies of OSe compound <b>19</b> showed the most promising inhibitory potential toward the JAK1 and STAT3 target receptors, with binding scores and interactions exceeding that of the cocrystallized inhibitor of JAK1.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645814","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":"Strategies for the Discovery and Design of Tissue Plasminogen Activators: Insights Into Bioengineering Objectives","authors":"Amirhossein Akbarpour Arsanjani,&nbsp;Davood Rabiei Faradonbeh,&nbsp;Ziba Veisi Malekshahi,&nbsp;Bashir Mosayyebi,&nbsp;Babak Negahdari","doi":"10.1002/ddr.70072","DOIUrl":"https://doi.org/10.1002/ddr.70072","url":null,"abstract":"<div>\u0000 \u0000 <p>Tissue plasminogen activators (tPAs) are critical in fibrinolysis and have become central to treating thrombotic disorders, including heart attacks, strokes, and pulmonary embolisms. Despite their efficacy, challenges such as bleeding complications, limited fibrin specificity, and rapid clearance necessitate the discovery of novel tPAs and the engineering of improved variants. This review highlights strategies for the discovery of tPAs from natural sources, including human, bacterial, venom-derived, and bat saliva-derived agents, as well as enzyme engineering approaches that enhance functional characteristics such as half-life, fibrin specificity, resistance to inhibitors, and clot penetration. Furthermore, this review explores alternative therapeutic approaches independent of tPAs, focusing on nonplasminogen activator agents and strategies that target platelets. By addressing current challenges and identifying future opportunities, this review provides a comprehensive perspective on advancing thrombolytic therapies through innovative discovery and design strategies.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602521","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":"A Novel Oxo-Palmatine Derivative 2q as Potent Reversal Agents Against Alzheimer's Disease","authors":"Shuo Pang,&nbsp;Zhuo Li,&nbsp;Ao Liu,&nbsp;Zhuo-Hui Luo,&nbsp;Heqing Yin,&nbsp;Songqiao Fan,&nbsp;Junjie Shi,&nbsp;Ning Liu,&nbsp;Shuo Pan,&nbsp;Ya-Jun Yang,&nbsp;Guo-jun Zhang,&nbsp;Jun Chen","doi":"10.1002/ddr.70073","DOIUrl":"https://doi.org/10.1002/ddr.70073","url":null,"abstract":"<div>\u0000 \u0000 <p>Palmatine (PAL), as an active ingredient in traditional Chinese medicine, had been demonstrated efficacy in ameliorating the manifestations of AD. Our research group has previously designed and synthesized the novel oxo-PAL derivative <b>2q</b> and found that it has exhibited notable neuroprotective properties. However, compound <b>2q</b> therapeutic impact on AD remains uncertain. In the current investigation, our findings demonstrated that compound <b>2q</b> displayed significant anti-AβOs activity in vitro by using xCELLigence analysis, and showed a high likelihood of crossing the blood-brain barrier. Furthermore, administration of compound <b>2q</b> yielded a notable amelioration in Aβ accumulation and hyperphosphorylation of Tau in 3×Tg mice. Additionally, it was observed that compound <b>2q</b> potentially enhanced the pathological characteristics of AD by targeting Potassium/Sodium Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 (HCN2). In conclusion, compound <b>2q</b> emerged as a promising candidate for AD treatment, as it effectively restored AD-associated pathological impairments. Furthermore, it has been identified as a potential target of HCN2, thereby offering novel avenues for the development of treatments for AD.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602522","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":"Linear Antimicrobial Peptide, Containing a Diindolyl Methane Unnatural Amino Acid, Potentiates Gentamicin Against Methicillin-Resistant Staphylococcus aureus","authors":"Shalini Singh,&nbsp;Grace Kaul,&nbsp;Manjulika Shukla,&nbsp;Abdul Akhir,&nbsp;Shubhandra Tripathi,&nbsp;Abhinav Gupta,&nbsp;Rakhi Bormon,&nbsp;Nisanth N. Nair,&nbsp;Sidharth Chopra,&nbsp;Sandeep Verma","doi":"10.1002/ddr.70070","DOIUrl":"https://doi.org/10.1002/ddr.70070","url":null,"abstract":"<div>\u0000 \u0000 <p>The headway for the management of emerging resistant microbial strains has become a demanding task. Over the years, antimicrobial peptides (AMP), have been recognized and explored for their highly systematized SAR and antibacterial properties. With this background, we have reported a new class of AMPs. These peptides incorporate an unnatural amino acid, with a motivation from cruciferous bioactive phytochemical bisindoles methane derivatives with highly selective antimicrobial action. These peptides may also be considered as linear derivatives of hirsutide isolated from entomopathogenic fungus. The synthesized peptides were tested for their antimicrobial activity against an ESKAPE pathogen panel, where peptide <b>3</b> exhibited equipotent MIC and potent synergistic action along with gentamicin against <i>Staphylococcus aureus</i> and <i>Enterococcus</i> clinical isolates. This combination was also able to repotentiate gentamicin against NRS119, a gentamicin-resistant MRSA. Molecular dynamics study and free energy calculations provided insights to membrane disruptive properties of AMP action, which assisted gentamicin pass through the lipid–water interface.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530462","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":"Multifunctional Docetaxel Cholesterol-Polyethylene Glycol Co-Modified Poly (N-Butyl) Cyanoacrylate Nanoparticles for Brain Tumor Therapy","authors":"Xiao Hu,&nbsp;Feifei Yang,&nbsp;Yonghong Liao,&nbsp;Lin Li,&nbsp;Lan Zhang","doi":"10.1002/ddr.70069","DOIUrl":"https://doi.org/10.1002/ddr.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Owing to the presence of the blood-brain barrier and the lack of significant specificity towards tumor cells after entry into the brain, the unsuccessful delivery of anticancer drugs to the treatment of brain tumors. The hypothesis that cholesterol-PEG co-modified poly (N-butyl) cyanoacrylate nanoparticles (CLS-PEG NPs) are an effective carrier for the treatment of brain tumors was verified, and the mechanism of its treatment for brain tumors was preliminarily explored. In this study, we used multifunctional poly (N-butyl) cyanoacrylate nanoparticles modified with cholesterol and polyethylene glycol (PEG) as a drug delivery system to encapsulate the anticancer drug docetaxel (DTX). Cell anti-proliferation tests showed that CLS-PEG NPs increased the inhibitory effect of DTX. A pharmacokinetic study indicated that CLS-PEG NPs achieved sustained release for 8 h. These experimental results demonstrated that CLS-PEG NPs amplified the concentration of the drug transported to the brain and sustained drug release in the brain. In addition, CLS-PEG NPs led to better pharmacological efficacy in an orthotopic brain glioma rat model. The survival rate of rats in the CLS-PEG NPs group was significantly prolonged to 28 d. We also found that CLS-PEG NPs inhibited M2 microglial polarization. These results indicate that CLS-PEG NPs are a prospective drug delivery system for targeting brain tumors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497332","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}