Drug Delivery and Translational Research最新文献_第2页

Macrophages co-loaded with drug-associated and superparamagnetic nanoparticles for triggered drug release by alternating magnetic fields. 巨噬细胞与药物相关和超顺磁性纳米颗粒共载，通过交变磁场触发药物释放。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-13 DOI: 10.1007/s13346-024-01774-9

Omkar Desai, Sandhya Kumar, Mario Köster, Sami Ullah, Sushobhan Sarker, Valentin Hagemann, Mosaieb Habib, Nicole Klaassen, Silke Notter, Claus Feldmann, Nina Ehlert, Hansjörg Hauser, Dagmar Wirth

{"title":"Macrophages co-loaded with drug-associated and superparamagnetic nanoparticles for triggered drug release by alternating magnetic fields.","authors":"Omkar Desai, Sandhya Kumar, Mario Köster, Sami Ullah, Sushobhan Sarker, Valentin Hagemann, Mosaieb Habib, Nicole Klaassen, Silke Notter, Claus Feldmann, Nina Ehlert, Hansjörg Hauser, Dagmar Wirth","doi":"10.1007/s13346-024-01774-9","DOIUrl":"10.1007/s13346-024-01774-9","url":null,"abstract":"Two features of macrophages make them attractive for targeted transport of drugs: they efficiently take up a broad spectrum of nanoparticles (NPs) and, by sensing cytokine gradients, they are attracted to the sites of infection and inflammation. To expand the potential of macrophages as drug carriers, we investigated whether macrophages could be simultaneously coloaded with different types of nanoparticles, thus equipping individual cells with different functionalities. We used superparamagnetic iron oxide NPs (SPIONs), which produce apoptosis-inducing hyperthermia when exposed to an alternating magnetic field (AMF), and co-loaded them on macrophages together with drug-containing NPs (inorganic-organic nanoparticles (IOH-NPs) or mesoporous silica NPs (MSNs)). We show that individual macrophages can take up both SPIONs and drug-loaded NPs efficiently, thereby generating drug-loaded cells susceptible to AMF-induced cell death. Macrophages co-loaded with SPIONs and drug-containing IOH-NPs spontaneously released the drugs at similar rates irrespective of the application of an AMF. Notably, while the spontaneous drug release from macrophages co-loaded with SPIONs and drug-associated MSNs was low, AMF exposure accelerated the drug release. Thus, AMF exposure of SPION/drug-MSN coloaded macrophages provides a simple strategy for trigger-controlled drug release since it does not require any chemical modification of NPs or drugs. Thus, we assume that the coloading of different types of NPs will expand the potential of macrophages for drug delivery.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2779-2793"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nanostructured lipid carriers for enhanced batimastat delivery across the blood-brain barrier: an in vitro study for glioblastoma treatment. 纳米结构脂质载体增强batimastat通过血脑屏障输送：胶质母细胞瘤治疗的体外研究

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-06 DOI: 10.1007/s13346-024-01775-8

Miguel Horta, Paula Soares, Bruno Sarmento, Catarina Leite Pereira, Raquel T Lima

{"title":"Nanostructured lipid carriers for enhanced batimastat delivery across the blood-brain barrier: an in vitro study for glioblastoma treatment.","authors":"Miguel Horta, Paula Soares, Bruno Sarmento, Catarina Leite Pereira, Raquel T Lima","doi":"10.1007/s13346-024-01775-8","DOIUrl":"10.1007/s13346-024-01775-8","url":null,"abstract":"Glioblastoma presents a significant treatment challenge due to the blood-brain barrier (BBB) hindering drug delivery, and the overexpression of matrix metalloproteinases (MMPs), which promotes tumor invasiveness. This study introduces a novel nanostructured lipid carrier (NLC) system designed for the delivery of batimastat, an MMP inhibitor, across the BBB and into the glioblastoma microenvironment. The NLCs were functionalized with epidermal growth factor (EGF) and a transferrin receptor-targeting construct to enhance BBB penetration and entrapment within the tumor microenvironment. NLCs were prepared by ultrasonicator-assisted hot homogenization, followed by surface functionalization with EGF and the construct though carbodiimide chemistry. The construct was successfully conjugated with an efficiency of 81%. Two functionalized NLC formulations, fMbat and fNbat, differing in the surfactant amount, were characterized. fMbat had a size of 302 nm, a polydispersity index (PDI) of 0.298, a ζ-potential (ZP) of -27.1 mV and an 85% functionalization efficiency (%FE), whereas fNbat measured 285 nm, with a PDI of 0.249, a ZP of -28.6 mV and a %FE of 92%. Both formulations achieved a drug loading of 0.42 μg/mg. In vitro assays showed that fNbat was cytotoxic and failed to cross the BBB, while fMbat showed cytocompatibility at concentrations 10 times higher than the drug's IC50. Additionally, fMbat inhibited MMP-2 activity between 11 and 62% across different cell lines and achieved a three-fold increase in BBB penetration upon functionalization. Our results suggest that the fMbat formulation has potential for enhancing GB treatment by overcoming current drug delivery limitations and may be combined with other therapeutic strategies for improved outcomes.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2794-2813"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Construction of folic acid modified fluoro-liposomes for oral delivery of erastin to achieve targeted anti-tumor therapy. 叶酸修饰氟脂质体的构建，用于口服擦除素实现靶向抗肿瘤治疗。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-03 DOI: 10.1007/s13346-024-01783-8

Min Hong, Xiaoyan Liu, Qinghong Ji, Mengyao Ou, Qiaoli Yue, Shuang Cheng

{"title":"Construction of folic acid modified fluoro-liposomes for oral delivery of erastin to achieve targeted anti-tumor therapy.","authors":"Min Hong, Xiaoyan Liu, Qinghong Ji, Mengyao Ou, Qiaoli Yue, Shuang Cheng","doi":"10.1007/s13346-024-01783-8","DOIUrl":"10.1007/s13346-024-01783-8","url":null,"abstract":"Erastin, as an effective ferroptosis inducer, has received extensive attention in anti-tumor research. To develop an oral nanocarrier for high efficient loading hydrophobic erastin, here we prepared a fluoro-liposome (FA-3 F-LS) by the self-assembly of the folic acid modified fluorinated amphiphiles-FA-3 F conjugates. The hydrophobic component of three perfluorooctyl chains endows the FA-3 F-LSs with high stability to resist the harsh gastrointestinal tract condition. Folic acids conjugated on the surface of FA-3 F-LSs ensure the better tumor targeting and higher oral bioavailability (32.1%) of erastin-loaded FA-3 F-LSs (erastin@FA-3 F-LSs) than free erastin (8.98%). As targeted anti-tumor nanomedicines, erastin@FA-3 F-LSs effectively inhibited the tumor cell proliferation in vitro by inducing ferroptosis through enhancing the glutathione (GSH) depletion, lipid peroxidation and generation of reactive oxygen species. In vivo studies demonstrated that FA-3 F-LSs displayed excellent application potential as a tumor-targeted oral drug delivery nanocarrier to depress the tumor growth with the loaded chemotherapeutic agents.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2848-2861"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A game of hide-and-seek: how extracellular vesicles evade the immune system. 一个捉迷藏的游戏：细胞外囊泡如何逃避免疫系统。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-22 DOI: 10.1007/s13346-025-01789-w

Bartika Ghoshal, Siddharth Jhunjhunwala

{"title":"A game of hide-and-seek: how extracellular vesicles evade the immune system.","authors":"Bartika Ghoshal, Siddharth Jhunjhunwala","doi":"10.1007/s13346-025-01789-w","DOIUrl":"10.1007/s13346-025-01789-w","url":null,"abstract":"Extracellular vesicles (EVs) are heterogeneously sized, cell-derived nanoparticles operating as proficient mediators of intercellular communication. They are produced by normal as well as diseased cells and carry a variety of cargo. While the molecular details of EV biology have been worked out over the past two decades, one question that continues to intrigue many is how are EVs able to evade the phagocytic immune cells while also being effectively internalized by the target cell or tissue. While some of the components that facilitate this process have started to be identified, many mechanisms are yet to be dissected. This review summarises some of the key mechanisms that cancer cell-derived and viral infected cell-derived EVs utilize to evade the immune system. It will discuss the diverse cloaking mechanisms, in the form of membrane proteins and cargo content that these EVs utilize to enhance pathogenesis. Further, it will highlight the different strategies that have been used to design EVs to escape the immune system, thereby increasing their circulation time with no major toxic effects in vivo. An understanding of the potential EV components that allow better immune evasion can be used to bioengineer EVs with better circulation times for therapeutic purposes.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2624-2642"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel preparation of pH-responsive hydrogel with chitosan-based microbeads for targeted oral delivery of bevacizumab to enhanced apoptosis in azoxymethane-induced colorectal cancer: cellular and in vivo mice models. 新型壳聚糖微球ph响应水凝胶的制备，用于靶向口服贝伐单抗，以增强偶氮甲烷诱导的结直肠癌的细胞凋亡：细胞和体内小鼠模型。

IF 5.5 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 DOI: 10.1007/s13346-025-01928-3

Tao You, Jian Chen, Yuesheng Zhu, Na Shan, Zejun Gao, Yao Shen, Yaojun Yu

{"title":"Novel preparation of pH-responsive hydrogel with chitosan-based microbeads for targeted oral delivery of bevacizumab to enhanced apoptosis in azoxymethane-induced colorectal cancer: cellular and in vivo mice models.","authors":"Tao You, Jian Chen, Yuesheng Zhu, Na Shan, Zejun Gao, Yao Shen, Yaojun Yu","doi":"10.1007/s13346-025-01928-3","DOIUrl":"https://doi.org/10.1007/s13346-025-01928-3","url":null,"abstract":"The number of colorectal cancer (CRC) cases is rising among younger people, making it the second most common cancer worldwide. A pH-responsive hydrogel containing chitosan-based microbeads (BHCMB) is proposed for the targeted oral delivery of bevacizumab as a potential treatment for CRC. The structural and functional properties of BHCMB formulations were validated through characterization via FTIR and XPS analyses. Investigations of in vitro drug release by hydrogels have demonstrated their responsiveness to pH variations, facilitating accurate dosing in physiological conditions. The HCT-116 colorectal cancer cell line was utilized to assess the in vitro anti-cancer properties of BHCMB hydrogel formulations. At 50 µg/mL, BHCMB significantly reduced cell growth and caused apoptosis by damaging mitochondrial membranes and generating reactive oxygen species (ROS). The gene expression analysis revealed that BHCMB treatment significantly downregulated COX-2, IL-6, and BCL2 levels, while markedly upregulating p53 and Bax expression. Additionally, protein analysis in HCT-116 cells confirmed increased Bax and cleaved caspase-3 levels alongside reduced BCL2, indicating enhanced pro-apoptotic activity and potential anti-tumor effects in CRC. The in vivo study illustrates the efficacy of the BHCMB hydrogel in inhibiting CRC growth in a mice model. This research proposes an innovative pH-responsive hydrogel system for the oral administration of bevacizumab. The aim was to attain precise drug release at the colorectal tumor site, thereby enhancing apoptosis and effectively hindering CRC progression.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oral delivery of dihydroartemisinin for the treatment of melanoma via bovine milk exosomes. 经牛乳外泌体口服双氢青蒿素治疗黑色素瘤。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-07 DOI: 10.1007/s13346-024-01785-6

Dulla Naveen Kumar, Aiswarya Chaudhuri, Deepa Dehari, Armin M Gamper, Dinesh Kumar, Ashish Kumar Agrawal

{"title":"Oral delivery of dihydroartemisinin for the treatment of melanoma via bovine milk exosomes.","authors":"Dulla Naveen Kumar, Aiswarya Chaudhuri, Deepa Dehari, Armin M Gamper, Dinesh Kumar, Ashish Kumar Agrawal","doi":"10.1007/s13346-024-01785-6","DOIUrl":"10.1007/s13346-024-01785-6","url":null,"abstract":"Cancer, particularly skin cancer, is a major cause of mortality worldwide, with melanoma being one of the most aggressive and challenging to treat types. Current therapeutic options, such as dacarbazine (DTIC), have limitations due to dose-related toxicities like liver toxicity. Therefore, there is a need for new and effective treatments for melanoma. Dihydroartemisinin (DHA), derived from artemisinin compounds known for their anti-malarial properties, has shown promise as an anti-cancer agent. However, the clinical use of DHA faces challenges such as low solubility and toxicity, which limit its therapeutic efficacy. To overcome these challenges, we developed an exosomal formulation of DHA to enhance its anti-cancer activity and reduce metastasis. Exosomes, biological vesicles, contain many biological macromolecules such as DNA, RNAs, and many other proteins, involved in intercellular communication, were isolated and loaded with DHA using the sonication method. The loaded exosomes were characterized for size (90-103 nm), polydispersity index (PDI: 0.119-0.123), and zeta potential (-23 to -28 mV). In vitro studies demonstrated the efficacy of DHA-loaded exosomes through cytotoxicity and apoptosis assays. The molecular mechanism of action was further elucidated using immunoblotting analysis, focusing on key proteins involved in apoptosis and metastasis regulation, including Bax, Bcl-2, survivin, and MMP-9. Furthermore, we observed a significant improvement in oral bioavailability (2.8-fold) with the exosomal formulation and enhanced in vivo anti-cancer activity of DHA. Notably, treatment with Exo-DHA resulted in strong enhancement of tumor growth suppression and reduced melanoma cell metastasis compared to free DHA.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2862-2877"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

pH-sensitive nano-drug delivery systems dual-target endothelial cells and macrophages for enhanced treatment of atherosclerosis. ph敏感纳米药物递送系统双靶内皮细胞和巨噬细胞增强动脉粥样硬化的治疗。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-29 DOI: 10.1007/s13346-025-01791-2

Yiping Deng, Li Liu, Yao Li, Huan Ma, Chuang Li, Kexin Yan, Ji Tian, Chunhong Li

{"title":"pH-sensitive nano-drug delivery systems dual-target endothelial cells and macrophages for enhanced treatment of atherosclerosis.","authors":"Yiping Deng, Li Liu, Yao Li, Huan Ma, Chuang Li, Kexin Yan, Ji Tian, Chunhong Li","doi":"10.1007/s13346-025-01791-2","DOIUrl":"10.1007/s13346-025-01791-2","url":null,"abstract":"Atherosclerosis (AS) is a chronic inflammatory disease characterized by vascular endothelial dysfunction. In the early stage of the disease, endothelial cell injury induces the infiltration of inflammatory macrophages, which secrete large amounts of inflammatory factors, further aggravating endothelial cell dysfunction and exacerbating the disease. Therefore, it is promising for co-targeting endothelial cells and macrophages further regulating the inflammatory microenvironment and endothelial cell function for effective treatment. The current nano-drug delivery system (NDDS) for AS treatment is mainly focused on anti-inflammatory therapy, while ignoring the potential value of suppressing inflammation and simultaneously improving vascular endothelial function. In this study, a pH-responsive dual-targeted NDDS based on plaque microenvironment, BC@CS/cRGD NPs, was prepared by combining baicalin (BC) with chondroitin sulfate (CS) through amidation reaction, and further modified with a targeting group cRGD peptide. In vitro release experiments illustrated a faster release of the nanoparticle at pH 5.0 than at pH 7.4. Meanwhile, in vitro cellular experiments demonstrated its ability to target activated endothelial cells and macrophages. In a mouse model of AS, BC@CS/cRGD NPs accumulated at plaque sites and effectively attenuated the plaque progression. In conclusion, this pH-sensitive BC@CS/cRGD NPs offered a very potential strategy for modulating endothelial dysfunction and inflammatory microenvironment for the treatment of AS.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2924-2940"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methacrylated poly(glycerol sebacate) as a photocurable, biocompatible, and biodegradable polymer with tunable degradation and drug release kinetics. 甲基丙烯酸酯聚甘油癸二酸酯是一种光固化、生物相容性和可生物降解的聚合物，具有可调节的降解和药物释放动力学。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2024-12-20 DOI: 10.1007/s13346-024-01762-z

Mei-Li L Bice, Marina H Yu, Valentina L Ortega, Chia-Chien Hsu, Kevin J McHugh

{"title":"Methacrylated poly(glycerol sebacate) as a photocurable, biocompatible, and biodegradable polymer with tunable degradation and drug release kinetics.","authors":"Mei-Li L Bice, Marina H Yu, Valentina L Ortega, Chia-Chien Hsu, Kevin J McHugh","doi":"10.1007/s13346-024-01762-z","DOIUrl":"10.1007/s13346-024-01762-z","url":null,"abstract":"Poly(glycerol sebacate) (PGS) is a biodegradable, elastomeric polymer that has been explored for applications including tissue engineering, drug delivery, and wound repair. Despite its promise, its biomedical utility is limited by its rapid, and largely fixed, degradation rate. Additionally, its preparation requires prolonged curing at high temperatures, rendering it incompatible with heat-sensitive molecules, complex device geometries, and high-throughput production. In this study, we synthesized methacrylated PGS (PGS-M), imparting the ability to rapidly photocross-link the polymer. Increasing the degree of methacrylation was found to slow PGS-M degradation; PGS-M (5.5 kDa) disks with 21% methacrylation lost 40.1 ± 11.8% of their mass over 11 weeks in vivo whereas 47% methacrylated disks lost just 14.3 ± 1.4% of their mass over the period. Daunorubicin release from PGS-M occurred in a linear fashion without a substantial initial burst. Further, increasing the degree of methacrylation extended the release of encapsulated drug. After 60 days, 21%, 27%, and 47% methacrylated disks with the same drug loading (w/w) released 56.8 ± 5.4%, 15.1 ± 0.4%, and 15.4 ± 0.3% of encapsulated drug, respectively. Importantly, the 27% and 47% methacrylated disks consistently released ~ 0.25% (w/w) of encapsulated drug per day with no burst release. Histological evaluation also suggested that PGS-M is biocompatible, eliciting limited inflammation and fibrous encapsulation when implanted subcutaneously. This report presents the first long-term in vitro studies and first in vivo studies using PGS-M and demonstrates the ability to tune PGS-M degradation rate, use PGS-M to encapsulate drug, and obtain sustained drug release over months.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2694-2709"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

When conventional approach in toxicity assays falls short for nanomedicines: a case study with nanoemulsions. 当传统的毒性分析方法不能用于纳米药物时：纳米乳剂的案例研究。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-08 DOI: 10.1007/s13346-024-01776-7

Ines Nikolić, Jelena Đoković, Dora Mehn, Giuditta Guerrini, Snežana Savić, Olivier Jordan, Gerrit Borchard

{"title":"When conventional approach in toxicity assays falls short for nanomedicines: a case study with nanoemulsions.","authors":"Ines Nikolić, Jelena Đoković, Dora Mehn, Giuditta Guerrini, Snežana Savić, Olivier Jordan, Gerrit Borchard","doi":"10.1007/s13346-024-01776-7","DOIUrl":"10.1007/s13346-024-01776-7","url":null,"abstract":"The aim of this study was to assess the critical quality attributes of parenteral nanoemulsion formulations by measuring several physicochemical parameters and linking them to their in vitro performance, illustrating how simplistic and routinely used approaches are insufficient for understanding a potential nanomedicine. Physicochemical characterization should encompass size and size distribution through at least two orthogonal techniques, such as dynamic light scattering (DLS) and electron microscopy, with added value from analytical ultracentrifugation. In vitro toxicity assessment was performed using three different assays to determine mitochondrial activity (WST-1), membrane integrity (lactate dehydrogenase release (LDH) assay), and cell viability (propidium iodide (PI) staining). Special focus was placed on estimating appropriate incubation times for relevant results in biological investigations. All formulations had an average diameter of around 100 nm. Conclusions regarding in vitro safety were assay-dependent: LDH and PI-based assays showed good correlation, while the WST-1 assay indicated that the non-PEGylated formulation altered mitochondrial activity more significantly compared to the PEGylated ones. The study underlined that the selection of appropriate cytotoxicity assays should be based on the possible mechanism of cellular perturbation. Alternatively, different aspects of cellular toxicity should be tested. Additionally, there is a need for well-designed controls to overcome nanoparticle scattering effects and avoid potentially false high toxicity results, which was demonstrated. Combining orthogonal, well-designed physicochemical and biological assays in a standardized manner as an initial step in the reliable preclinical characterization of nanomedicines is suggested. This represents a key aspect of new methodologies in nanomedicine characterization.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2814-2832"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Robust peptide/RNA complexes prepared with microfluidic mixing for pulmonary delivery by nebulisation. 用微流体混合制备的强效肽/RNA复合物，用于雾化肺输送。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-18 DOI: 10.1007/s13346-024-01773-w

Cheng Ma, Michael Y T Chow, Chengyang Zhang, Paulina Goldbaum, Jamie Chien-Ming Hsieh, Jenny K W Lam

{"title":"Robust peptide/RNA complexes prepared with microfluidic mixing for pulmonary delivery by nebulisation.","authors":"Cheng Ma, Michael Y T Chow, Chengyang Zhang, Paulina Goldbaum, Jamie Chien-Ming Hsieh, Jenny K W Lam","doi":"10.1007/s13346-024-01773-w","DOIUrl":"10.1007/s13346-024-01773-w","url":null,"abstract":"Small interfering RNA (siRNA) and messenger RNA (mRNA) have drawn considerable attention in recent years due to their ability to modulate the expression of specific disease-related proteins. However, it is difficult to find safe, robust, and effective RNA delivery systems suitable for pulmonary delivery to treat lung diseases. In this study, two cationic peptides, namely LAH4-L1 and PEG12KL4, were employed as non-viral vectors for siRNA and mRNA delivery. Four formulations (i.e. LAH4-L1/siRNA; PEG12KL4/siRNA; LAH4-L1/mRNA and PEG12KL4/mRNA) were investigated. Microfluidic mixing method was utilised to fabricate RNA complexes in a controllable and reproducible manner. Upon optimisation of the microfluidic mixing protocol, a vibrating mesh nebuliser was employed to aerosolise the RNA complexes, and their transfection efficiency was evaluated on A549 and BEAS-2B cells. Following nebulisation, inhalable mist was generated for all RNA formulations with mass median aerodynamic diameter below 5 μm. Although the hydrodynamic particle sizes of the RNA complexes were significantly reduced to around 100 nm after nebulisation regardless of the original size of the complexes prior to nebulisation, the RNA binding efficiency and the in vitro RNA transfection ability of all the peptide formulations were successfully preserved with no significant differences compared to the same system before nebulisation. The current result indicates that both LAH4-L1 and PEG12KL4 hold significant potential for future clinical application for pulmonary siRNA and mRNA delivery through nebulisation.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2765-2778"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0