International Journal of Nanomedicine最新文献

{"title":"How Advanced Are Exosomes as Cell-Free Therapeutics for Spinal Cord Injury?","authors":"Yaqi Wu, Yu Wang, Jun Zhou, Zhijian Tang, Lulu Huang, Shengwen Liu","doi":"10.2147/IJN.S536652","DOIUrl":"10.2147/IJN.S536652","url":null,"abstract":"<p><p>Spinal cord injury (SCI) remains a leading cause of disability worldwide, characterized by complex pathophysiological processes involving primary mechanical damage and secondary cascades of inflammation, oxidative stress, and gliosis. Current cell-based therapies face challenges such as low survival rates, tumorigenicity, and immune rejection. Emerging evidence highlights exosomes-nanoscale extracellular vesicles derived from various cell types-as promising cell-free therapeutic agents. These exosomes mediate intercellular communication by transferring bioactive cargo and exhibit advantages such as low immunogenicity, stability, and blood-spinal cord barrier permeability. This review explores the neuroprotective roles of exosomes from diverse cellular sources in SCI repair. Key mechanisms include regulation of macrophage/microglia polarization, suppression of pyroptosis, promotion of vascularization, inhibition of glial scar formation and enhancement of axonal growth. Challenges remain in optimizing exosome yield, standardization, and clinical translation. Future directions emphasize multi-target therapies, biomarker exploration, and hybrid approaches combining exosomes from multiple. A combination of exosomes with biomaterials or stem cells would amplify the therapeutic effects and reduce the dosage of exosomes. This review underscores the potential of exosome-based therapies to revolutionize SCI treatment by addressing its multifaceted pathophysiology while circumventing risks associated with cell transplantation.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11669-11683"},"PeriodicalIF":6.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185862","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":"Effect Analysis of Extracellular Vesicles in the Treatment of Bronchopulmonary Dysplasia via Different Drug Delivery and Administration Routes.","authors":"Wanting Xu, Siyu Chen, Ting Liang, Lan Kang, Qinxin Zheng, Yan Yang, Ling Guo, Jing Liu, Rong Zhang, Wenbin Dong","doi":"10.2147/IJN.S530819","DOIUrl":"10.2147/IJN.S530819","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are emerging as nanoscale, cell-free therapeutics for bronchopulmonary dysplasia (BPD), a chronic lung disease in premature infants characterized by underdeveloped alveoli and abnormal blood vessel formation. This review exhibits how different EV delivery methods influence therapeutic effects in BPD. Intra-tracheal administration of EVs enables localized pulmonary delivery, which may improve treatment efficiency via reducing inflammation and promoting lung development. Intravenous delivery provides systemic anti-inflammatory effects requiring higher doses because of lung's blood vessel barriers. Intraperitoneal administration requires higher dosages to produce comparable effects and shows lower drug accumulation in the lungs. Intragastric administration often results in poor absorption due to the digestive environment. The distribution of EVs in the body is largely dependent on delivery methods. Nebulized and tracheal administrated EVs primarily concentrate in the lungs, whereas intravenous EVs tend to distribute in the liver and spleen. Mechanistically, EVs reduce oxidative stress and cell damage by influencing important biological pathways like TGF-β1/Smad3 and PTEN/PI3K/Akt. Although previous studies in neonatal animal models demonstrated that EVs are safe and promising, clinical translation of EVs requires standardized production, optimized dosage, non-invasive administration method, and long-term safety verification. Future efforts are suggested to focus on neonate targeting, biomarker-guided clinical trials of EVs in treating BPD.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11617-11645"},"PeriodicalIF":6.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185743","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":"The Role of Piezoelectric Materials in Bone Remodeling and Repair: Mechanisms and Applications.","authors":"Wenjie Yue, Wanhao Zhang, Jing Zhang, Wenhe Qin, Xiaomei Bie, Yantao Zhao, Gang Xu","doi":"10.2147/IJN.S535976","DOIUrl":"10.2147/IJN.S535976","url":null,"abstract":"<p><p>Bones can sense bioelectricity. The process of bone remodeling and repair needs complex physiological signals like bioelectric, biochemical, and biomechanical factors, which work together to promote bone recovery. The formation, healing, and regeneration of natural bones are intricately linked to the influence of electrical signals. Piezoelectric materials have piezoelectric properties similar to bones, making them suitable for bone like repair. This study systematically summarizes the role of piezoelectric materials in bone remodeling and repair, as well as their related preparation techniques. Subsequently, the piezoelectric mechanism of bones is explored in depth, including the study of bone composition, analysis of piezoelectric and osteogenic mechanisms, and research progress on piezoelectric stimulation guided bone regeneration and repair. Through these analyses, the principle of how piezoelectric materials interact with bones to promote bone repair and remodeling has been further understood. Finally, the article analyzes the mechanism of piezoelectric materials on bone remodeling and repair, revealing how piezoelectric stimulation promotes bone regeneration and repair. These findings offer theoretical foundation and practical guidance for the further application of piezoelectric materials in orthopedics.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11593-11616"},"PeriodicalIF":6.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185845","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":"Polydopamine Dual-Modal Nanotherapy Synergizes Photothermal Antibacterial and Nanozyme Anti-Inflammatory Effects for Periodontitis Treatment.","authors":"Jun Guo, Yifan Liu, Yi Zhang, Yuyao Li, Yunlong Li, Jian Yang","doi":"10.2147/IJN.S533622","DOIUrl":"10.2147/IJN.S533622","url":null,"abstract":"<p><strong>Introduction: </strong>Given the limitations associated with clinical curettage in the treatment of periodontitis, there is a pressing need to enhance the complete removal of plaque from deep periodontal pockets and to facilitate the repair of periodontal tissues through appropriate medical interventions. Despite the significant advancements of various local drug delivery systems (LDDS) for the adjunctive treatment of periodontitis, their efficacy remains constrained by two intertwined challenges: inadequate antibiofilm capability and excessive reactive oxygen species (ROS)-mediated tissue damage.</p><p><strong>Methods: </strong>To simultaneously overcome these dual barriers, we synthesized polydopamine nanoparticles (PDA NPs) through a straightforward and efficient self-polymerization process of dopamine, followed by the synthesis of nanoparticles on the surface via reductive methods to create multifunctional nanoplatforms (PAg).</p><p><strong>Results: </strong>Notably, these PDA nanoparticles, which are based on comprehensive nanocomposites, function as photothermal agents that enhance the therapeutic efficacy against biofilms in vitro through antibacterial photothermal therapy (PTT) under near-infrared laser irradiation. Furthermore, owing to the enzyme-like activity of PDA nanozyme, the engineered nanocomposite is capable of effectively scavenging ROS in Raw267.4 cells and human periodontal ligament cells under oxidative stress conditions. The in vitro and in vivo analyses demonstrated that live/dead staining of the biofilm, along with Western blot assessments of inflammatory markers, substantially augmented the antibacterial and anti-inflammatory efficacy. The nano-platform-based PAg nanoparticles developed in our study not only markedly enhanced the antibacterial effect through combination therapy but also efficiently reduced cellular ROS via the enzyme-like activity of the nanozyme.</p><p><strong>Conclusion: </strong>This dual-modal nanotherapy delivers a coordinated attack on periodontitis pathogenesis, including direct physical elimination of biofilms coupled with ROS scavenging to mitigate collateral tissue damage, thereby addressing the limitations of current LDDS.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11505-11524"},"PeriodicalIF":6.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148952","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":"MXene-Mediated Nanocarrier Delivery Enhances the Chondroprotective Effects of Quercetin in Experimental Osteoarthritis.","authors":"Kaifeng Gan, Jie Li, Xuyang Zhang, Zhenhua Feng, Junhui Liu, Fengdong Zhao","doi":"10.2147/IJN.S540035","DOIUrl":"10.2147/IJN.S540035","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoarthritis (OA) is a common chronic joint disease that severely affects patients' quality of life. Quercetin, a natural flavonoid, exhibits chondroprotective effects, though its bioavailability through regular oral consumption is limited. In this study, we employed two-dimensional MXene nanosheets as a nanocarrier to facilitate targeted intracellular delivery of quercetin, aiming to enhance its therapeutic efficacy against OA.</p><p><strong>Methods: </strong>Methods: Porous Ti₃C₂Tₓ MXene nanosheets were synthesized via selective etching and then loaded with quercetin through physical adsorption. Material characterization was performed using transmission electron microscopy (TEM), scanning electron microscopy (SEM), ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), and in vitro release assays. For in vitro evaluation, IL-1β-stimulated primary mouse articular chondrocytes (ACs) were treated with free quercetin or MXene-loaded quercetin, followed by assessments of cell viability, apoptosis, cell cycle progression, migration, oxidative stress markers, and ferroptosis-related protein expression. For in vivo validation, a destabilization of the medial meniscus (DMM) mouse model of OA was established to assess cartilage morphology, ferroptosis markers, and histological changes after intra-articular injection of treatments.</p><p><strong>Results: </strong>MXene-loading significantly enhanced quercetin's protective effects in IL-1β-induced primary mouse ACs, including improved cell viability and proliferation, reduced apoptosis, alleviated oxidative stress, and suppression of ferroptosis. In OA mice, MXene-quercetin treatment more effectively preserved cartilage integrity and inhibited ferroptosis compared with free quercetin.</p><p><strong>Conclusion: </strong>These findings suggest that MXene can serve as a biocompatible carrier to improve quercetin delivery in osteoarthritis models, supporting its potential for further preclinical evaluation.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11553-11567"},"PeriodicalIF":6.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149019","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 of Drug-Loaded Microsphere Technology for Targeted Immunotherapy Against Prostate Cancer.","authors":"Wubing Feng","doi":"10.2147/IJN.S526247","DOIUrl":"10.2147/IJN.S526247","url":null,"abstract":"<p><p>Treating advanced prostate cancer presents challenges like therapy resistance and systemic toxicity. Combining drug-loaded microspheres with immunotherapy, such as PD-1 inhibitors, and targeted therapy like PARP inhibitors has transformed the treatment of prostate cancer. This review focuses on microcatheter-assisted techniques that allow for precise embolization using 100-300 μm microspheres and enable sustained drug release, resulting in an objective response rate (ORR) of 35-52% in clinical trials. Important advancements include pulsed injection protocols at 0.5 mL/min under cone beam CT (CBCT) guidance and biomarker-driven stratification, focusing on a PD-L1 combined positive score (CPS) of ≥10 and homologous recombination repair (HRR) mutations. The PROEMBOL trial shows a 98.1% rate of immediate hemostasis, and combination therapies with PARP inhibitors increase the median progression-free survival (PFS) to 14.2 months for patients with HRR mutations. Future efforts must prioritize standardized technical protocols and real-world validation of long-term outcomes.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11479-11489"},"PeriodicalIF":6.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148845","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":"Intravenous Delivery of Angiopep-Functionalized Polypropylenimine Dendriplex Enhances Gene Expression in the Brain.","authors":"Hawraa Ali-Jerman, Sukrut Somani, Zainab Al-Quraishi, Khadeejah Maeyouf, Mirna Merkler, Symeon Gerasimou, Rothwelle J Tate, Shuzo Sakata, Margaret Mullin, Craig Irving, Graeme J Anderson, Jessica R Bame, Graeme MacKenzie, Gayle McNeill, Christine Dufès","doi":"10.2147/IJN.S510487","DOIUrl":"10.2147/IJN.S510487","url":null,"abstract":"<p><strong>Background: </strong>The application of gene therapy for treating neurological disorders, including brain cancer, Parkinson's, and Alzheimer's disease, is significantly limited by the current shortage of gene vectors that can effectively cross the blood-brain barrier (BBB) following intravenous administration. Recent studies demonstrated that angiopep-2 can enhance the delivery of therapeutic agents across the BBB through receptor-mediated endocytosis. This study therefore explores the potential of angiopep-2-conjugated generation-3 diaminobutyric polypropylenimine (DAB) dendrimer (DAB-Ang) as nanocarrier for brain-targeted gene delivery.</p><p><strong>Methods: </strong>Angiopep-2 was conjugated to DAB dendrimer and evaluated in terms of DNA condensation ability, particle size, surface charge, and structural morphology. The cellular uptake was studied in vitro using bEnd.3 brain endothelial cells, and the in vivo efficacy of DAB-Ang dendriplexes for brain gene expression was evaluated in BALB/c mice following intravenous administration.</p><p><strong>Results: </strong>DAB-Ang dendrimer successfully condensed up to 90% of DNA, forming stable spherical dendriplexes with sizes under 240 nm and positive zeta potentials. In vitro, DAB-Ang dendriplex achieved a 9-fold higher cellular uptake in brain endothelial cells in comparison to the unmodified complex, predominantly through clathrin-mediated endocytosis and macropinocytosis. In vivo studies showed significantly increased gene expression in the brain following DAB-Ang dendriplex treatment, achieving 1.8-fold and 3.2-fold higher expression in comparison to DAB dendriplex and naked DNA, respectively, with minimal off-target effects.</p><p><strong>Conclusion: </strong>Angiopep-2-conjugated DAB dendrimer demonstrated high specificity and efficacy in facilitating gene delivery to the brain, offering a promising platform for therapeutic applications in neurological disorders.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11569-11591"},"PeriodicalIF":6.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148850","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":"How TiO₂ Nanomaterials are Emerging as Key Therapeutics in Stomatology.","authors":"Junnan Qi, Huimin Liu, Huen Li, Haofeng Liu, Yawen Wang, Chunru Kong, Li Fu, Bei Chang","doi":"10.2147/IJN.S533650","DOIUrl":"10.2147/IJN.S533650","url":null,"abstract":"<p><p>Conventional treatments for oral diseases-such as cancer and tissue defects-are often limited by high invasiveness, suboptimal efficacy, and drug resistance. In recent years, titanium dioxide (TiO₂) nanomaterials have demonstrated remarkable therapeutic potential in the field of oral medicine. This review systematically evaluates the current applications and future prospects of TiO₂ and its reduced form (TiO_2- _x) nanomaterials across six major domains: cancer diagnosis and therapy, antibacterial treatment, tissue regeneration, drug delivery, restorative dental materials, and teeth whitening, based on an extensive literature search of databases including PubMed and Web of Science. The findings reveal that TiO₂ nanomaterials exhibit exceptional multifunctionality through various mechanisms: (1) surface-enhanced Raman spectroscopy (SERS) substrates achieve 100% sensitivity and 95.83% specificity in diagnosing oral squamous cell carcinoma; (2) reactive oxygen species (ROS)-mediated antibacterial efficiency exceeds 99% against key oral pathogens; (3) modified implant surfaces show a 1.5-fold increase in bone-implant contact; and (4) the incorporation of only 0.06% TiO₂ nanoparticles enhances resin hardness by over 200%. Notably, TiO_2-x exhibits visible/near-infrared responsiveness, photothermal conversion capacity, and peroxidase-like activity, enabling 12% H₂O₂-based whitening outcomes comparable to commercial 40% H₂O₂ products. Collectively, TiO₂-based nanomaterials represent a paradigm shift toward precision oral medicine, owing to their excellent biocompatibility, multifunctional therapeutic mechanisms, and broad application potential. Nonetheless, successful clinical translation requires addressing critical challenges, including synthesis standardization, comprehensive biosafety evaluation, optimization of interfacial bonding strength, and the development of regulatory frameworks tailored to dental nanomedicine.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11451-11478"},"PeriodicalIF":6.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137537","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":"Novel Platelet-Like PLGA-PSP Nanoparticles Based on Platelet-Specific Peptides Alleviated Traumatic Hemorrhage.","authors":"Wenda Fu, Hua Wei, Dongxia Ren, Yan Zheng, Jin Zhang, Shijie Mu, Longfei Yang","doi":"10.2147/IJN.S539137","DOIUrl":"10.2147/IJN.S539137","url":null,"abstract":"<p><strong>Background: </strong>Platelets play a crucial role in regulating coagulation. However, balancing the supply and clinical demands of platelet concentrates is a tough challenge. It is urgent to explore a novel platelet substitute with biosafety and efficacy in traumatic hemorrhage.</p><p><strong>Methods: </strong>The platelet-like PLGA-PSP nanoparticles were synthesized by covalently coupling the linear platelet-specific peptides including CBP, VBP and FMP to the active carboxyl functional group of PLGA-PEG nanoparticles. The biosafety of the platelet-like PLGA-PSP nanoparticles was assessed. Subsequently, in vitro experiments were conducted to verify the effects of PLGA-PSP nanoparticles on platelet adhesion, aggregation and activation. Furthermore, the hemostatic efficacy of PLGA-PSP nanoparticles was confirmed in the tail vein, liver and femoral artery hemorrhage of normal and thrombocytopenic mice.</p><p><strong>Results: </strong>We successfully designed and synthesized the non-toxic PLGA-PSP nanoparticles with specific hemostatic ability that significantly induced platelet adhesion and aggregation without triggering unexpected platelet activation. Moreover, the application of PLGA-PSP nanoparticles was demonstrated to effectively reduce the bleeding time and blood loss in the tail vein, liver and femoral artery of both normal and thrombocytopenic mice.</p><p><strong>Conclusion: </strong>The novel platelet-like PLGA-PSP nanoparticles present a promising therapeutic option for the rapid hemostasis of traumatic hemorrhage based on the biosafety and efficacy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11491-11504"},"PeriodicalIF":6.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137594","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":"Anti-Arthritis and Biosafety Properties of Green Synthesized Zinc Oxide Nanoparticles Loaded with <i>Cedrus libani</i> Extract.","authors":"Diana Battal Mejjo, Ream Nayal, Wassim Abdelwahed, Mohammad Yaser Abajy","doi":"10.2147/IJN.S537934","DOIUrl":"10.2147/IJN.S537934","url":null,"abstract":"<p><strong>Purpose: </strong>This research was conducted to develop an easy and safe method for synthesizing zinc oxide nanoparticles (ZnO NPs) with the aim of enhancing the efficacy and biosafety of ethanolic <i>Cedrus libani</i> (CL) extract and its aqueous fraction (ACL), as a potential preclinical candidate for anti-arthritis applications.</p><p><strong>Methods: </strong>UV-visible spectrophotometry, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy analysis, dynamic light scattering, and zeta potential were used to characterize the synthesized ZnO NPs. The optimal synthesis conditions were determined by evaluating the effects of reaction parameters. The anti-arthritis effect was investigated in vitro using albumin denaturation and human red blood cells (HRBCs) membrane stabilization tests. Additionally, Franz cells were used to determine the ex vivo permeability; carrageenan-induced paw edema, C-reactive protein measurement, and erythrocyte sedimentation rate were used to study the in vivo anti-arthritis effect. Biosafety was assessed through acute and subacute dermal toxicity tests.</p><p><strong>Results: </strong>Both CL and ACL could synthesize ZnO NPs with 71 and 44 nm diameters, respectively. In vitro, synthesized ZnO NPs showed superior anti-arthritis effects compared to sodium diclofenac and plant extracts, with the IC₅₀ values for the albumin denaturation test being10.84 and 11.93 µg/mL for CL-ZnO NPs and ACL-ZnO NPs, respectively. The IC₅₀ values for the HRBCs membrane stabilization assay were 9.74 and 14.8 µg/mL for CL-ZnO NPs and ACL-ZnO NPs, respectively. The ex vivo permeability study showed high permeability (946.8 µg/h/cm²). In vivo, both synthesized ZnO NPs demonstrated significant inhibition of carrageenan-induced edema, and performed better than sodium diclofenac and plant extracts, with maximum inhibition of 85.96±14.21% (CL-ZnO NPs) and 92.97±6.43% (ACL-ZnO NPs). Acute and subacute toxicity evaluations revealed no adverse effects.</p><p><strong>Conclusion: </strong>The green synthesized ZnO NPs from both CL and ACL had high permeability, superior efficacy, and biosafe which make them a promising natural product for managing arthritis conditions.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11525-11551"},"PeriodicalIF":6.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137534","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}