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Nano-spanlastics-loaded dissolving microneedle patches for ketotifen fumarate: advanced strategies for allergic conjunctivitis treatment and molecular insights. 富马酸酮替芬的纳米跨膜载体可溶微针贴片:过敏性结膜炎治疗的先进策略和分子研究。
IF 5.5 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-09-01 Epub Date: 2025-02-11 DOI: 10.1007/s13346-025-01796-x
Sammar Fathy Elhabal, Mohamed El-Nabarawi, Mohamed Fathi Mohamed Elrefai, Mahmoud H Teaima, Mai S Shoela, Gehad M Khamis, Ahmed Mohsen Faheem, Nada Ahmed Kholeif, Mahmoud Tarek Sanad
{"title":"Nano-spanlastics-loaded dissolving microneedle patches for ketotifen fumarate: advanced strategies for allergic conjunctivitis treatment and molecular insights.","authors":"Sammar Fathy Elhabal, Mohamed El-Nabarawi, Mohamed Fathi Mohamed Elrefai, Mahmoud H Teaima, Mai S Shoela, Gehad M Khamis, Ahmed Mohsen Faheem, Nada Ahmed Kholeif, Mahmoud Tarek Sanad","doi":"10.1007/s13346-025-01796-x","DOIUrl":"10.1007/s13346-025-01796-x","url":null,"abstract":"<p><p>Allergic conjunctivitis (AC) is the most common inflammatory disease affecting the eye's ocular surface, lid, conjunctiva, and cornea. However, effective ocular drug delivery remains challenging due to physiological barriers such as the corneal barrier. Ketotifen (KF), a widely used antihistamine and mast cell stabilizer, for treating AC and atopic asthma but belongs to the Biopharmaceutical Classification System (BCS II) have poor solubility. This study developed a multiple strategies approach for the first time, utilizing the spanlastics nano-vesicular carriers' system (SP) containing KF using an ethanol injection method. The optimized KF-SP exhibited the smallest particle size, largest zeta-potential and entrapment efficiency ∼232.5 ± 1.9 nm, -28 ± 0.51 and 73 ± 0.02%, respectively were further incorporated into PVA/PVP polymeric dissolving microneedles (MNs) by using a micromolding technique. Scanning electron microscopy (SEM) analysis confirmed well-defined tips and morphology, and in vitro studies showed a controlled 93% cumulative release over 72 h, with a zero-order kinetic release profile, providing stable therapeutic levels. Pharmacodynamic evaluation using the Ovalbumin/Aluminium hydroxide-induced AC model demonstrated significant reductions in IgE, TNF-α, and IL-6 levels by 68.7%, 71.3%, and 67.6%, respectively, while TGF-β and IL-10 levels increased by 70.1% and 62.7% using ELISA (Enzyme-Linked Immunosorbent Assay). Gene expression analysis (IGF-1, Annexin A1, and Bcl2) further supported the therapeutic potential of this system. In this study, we proved the topical application of the multiple strategies approach KF-SP loaded PVA/PVP MNs patch offers a targeted, sustained release treatment for AC, with promising implications for prolonged ocular therapy.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3161-3184"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398633","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
Synthesis and characterization of chitosan-grafted-dopamine based micelles as multifunctional nanomedicines for Parkinson's disease treatment by intranasal administration. 经鼻给药治疗帕金森病的壳聚糖-多巴胺胶束多功能纳米药物的合成与表征
IF 5.5 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-09-01 DOI: 10.1007/s13346-025-01963-0
Adriana Trapani, Annalucia Carbone, Sante Di Gioia, Giuseppe Fracchiolla, Piera Soccio, Filippo Maria Perna, Andrea Francesca Quivelli, Gian Paolo Suranna, Roberto Grisorio, Chiara Lo Porto, Daniele Conelli, Giuditta Colangelo, Massimo Conese
{"title":"Synthesis and characterization of chitosan-grafted-dopamine based micelles as multifunctional nanomedicines for Parkinson's disease treatment by intranasal administration.","authors":"Adriana Trapani, Annalucia Carbone, Sante Di Gioia, Giuseppe Fracchiolla, Piera Soccio, Filippo Maria Perna, Andrea Francesca Quivelli, Gian Paolo Suranna, Roberto Grisorio, Chiara Lo Porto, Daniele Conelli, Giuditta Colangelo, Massimo Conese","doi":"10.1007/s13346-025-01963-0","DOIUrl":"https://doi.org/10.1007/s13346-025-01963-0","url":null,"abstract":"<p><p>The main aim of this work was to synthesize new chitosan amphiphilic derivatives able to self-assembly encapsulating substances acting at different target sites implicated in Parkinson disease (PD). For this purpose, O-carboxymethyl-chitosan (O-CMCS) was grafted with dopamine (DA) exploiting a carbodiimide mediated coupling reaction using different polymer/DA weight ratios. The structural characterization of the resulting O-CMCS-g-DA conjugates was carried out by spectral (i.e., ì FT-IR, <sup>1</sup>H-NMR spectroscopy) and potentiometric titrations. The physicochemical characterization of these conjugates was performed by thermal analysis, scanning electron microscopy coupled with energy dispersive X-ray spectroscopy. The in vitro DA release was carried out in simulated nasal fluid showing in any case a sustained release of the neurotransmitter. The amphiphilic O-CMCS-g-DA conjugate at highest substitution degree was allowed to form micelles using the dialysis method. The Critical Micellar Concentration of such micelles was determined by the conductometric method and resulted of 1 × 10<sup>- 4</sup> mg/mL Quercetin (QUE), selected as hydrophobic antioxidant model drug, was encapsulated into the core of these micelles with an efficiency of 18%. From a biological point of view, none of the O-CMCS-g-DA conjugates was cytotoxic against the target neuronal SH-SY5Y cells. Moreover, all the O-CMCS-g-DA conjugates were able to modulate neuroinflammation as demonstrated by mRNA expression level analysis. Therefore, these O-CMCS-g-DA based micelles showed a great potential as multifunctional nanomedicines for brain delivery by intranasal route of a lipophilic antioxidant involved in the oxidative stress together with the neurotransmitter DA exploiting a delivery system with modulating properties of neuroinflammation.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946587","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
Formulation and clinical translation of inhalable nanomedicines for the treatment and prevention of pulmonary infectious diseases. 用于治疗和预防肺部感染性疾病的可吸入纳米药物的配方和临床转化。
IF 5.5 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-09-01 Epub Date: 2025-04-29 DOI: 10.1007/s13346-025-01861-5
Rami Ahmed, Frederic Tewes, Marique Aucamp, Admire Dube
{"title":"Formulation and clinical translation of inhalable nanomedicines for the treatment and prevention of pulmonary infectious diseases.","authors":"Rami Ahmed, Frederic Tewes, Marique Aucamp, Admire Dube","doi":"10.1007/s13346-025-01861-5","DOIUrl":"10.1007/s13346-025-01861-5","url":null,"abstract":"<p><p>Pulmonary infections caused by bacteria, viruses and fungi are a significant global health issue. Inhalation therapies are gaining interest as an effective approach to directly target infected lung sites and nanoparticle-based pulmonary delivery systems are increasingly investigated for this purpose. In this review, we provide an overview of common pulmonary infectious diseases and review recent work on the application of inhalable nanoparticle-based formulations for pulmonary infectious diseases, the formulation strategies, and the current research for delivering inhalable nanomedicines. We also evaluate the current clinical development status, market landscape, and discuss challenges that impede clinical translation and propose solutions to overcome these obstacles, highlighting promising opportunities for future advancements in the field. Despite advancements made and products reaching the market, notable gap persists in translational research, with challenges in achieving the target product profile, availability of appropriate in vivo disease models, scale-up, and market related questions, likely hindering research translation to the clinic.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2967-2993"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997883","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
Construction of a thermosensitive gel based on hydroxypropyl-β-cyclodextrin/meloxicam inclusion complexes for improving meloxicam solubility and prolonging drug retention time in the cornea. 羟丙基-β-环糊精/美洛昔康包合物的构建改善美洛昔康溶解度和延长药物在角膜内滞留时间的热敏凝胶。
IF 5.5 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-09-01 Epub Date: 2025-01-23 DOI: 10.1007/s13346-025-01797-w
Lvyao Yang, Xiu'e Li, Yuanke Zhang, Jingjing Tian, Guixia Ling, Peng Zhang
{"title":"Construction of a thermosensitive gel based on hydroxypropyl-β-cyclodextrin/meloxicam inclusion complexes for improving meloxicam solubility and prolonging drug retention time in the cornea.","authors":"Lvyao Yang, Xiu'e Li, Yuanke Zhang, Jingjing Tian, Guixia Ling, Peng Zhang","doi":"10.1007/s13346-025-01797-w","DOIUrl":"10.1007/s13346-025-01797-w","url":null,"abstract":"<p><p>The eyes are easily stimulated by external factors, which can cause inflammation. Anti-inflammatory drugs are usually used to inhibit the production of inflammatory factors. Many nonsteroidal anti-inflammatory drugs have been used for the eye, but due to the poor solubility of meloxicam, there are currently no marketed meloxicam preparations for the treatment of eye diseases. This article uses hydroxypropyl-β-CD (HP-β-CD) to encapsulate meloxicam and combined with thermosensitive gel to prepare an HP-β-CD/meloxicam inclusion complex eye thermosensitive gel, which can improved the water solubility of meloxicam and extend the retention time of the drug in the cornea, and achieve the goal of slow release through continuous dissolution. It not only has the advantages of convenient administration and accurate dosage of eye drops, but also overcomes the disadvantage of easy loss of eye drops, showing the advantages of long retention time and fewer administration times, and provides a basis for the development of other dosage forms of meloxicam.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3185-3198"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028320","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
Asymmetric nanocapsules via elongated liposome templated polymerization (ELTP) mediated by RAFT polymerization. RAFT聚合介导的细长脂质体模板聚合(ELTP)制备非对称纳米胶囊。
IF 5.5 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-09-01 Epub Date: 2025-03-06 DOI: 10.1007/s13346-025-01805-z
Yunxin Xiao, Alexander W Jackson, Angel Tan, John F Quinn, Simon Crawford, Ben J Boyd
{"title":"Asymmetric nanocapsules via elongated liposome templated polymerization (ELTP) mediated by RAFT polymerization.","authors":"Yunxin Xiao, Alexander W Jackson, Angel Tan, John F Quinn, Simon Crawford, Ben J Boyd","doi":"10.1007/s13346-025-01805-z","DOIUrl":"10.1007/s13346-025-01805-z","url":null,"abstract":"<p><p>Polymeric nanocapsules comprised of hydrophobic shells and hollow aqueous interiors are an extremely useful class of nanomaterial, particularly in the encapsulation and controlled delivery of hydrophilic cargo. Generally prepared via droplet or latex templation approaches, polymeric nanocapsules are mostly spherical. Controlling the morphology of hollow nanocapsules is an intriguing design challenge. Non-spherical, or elongated, templates are often inorganic materials which do not directly impart a hollow interior, and their post-polymerization removal is not straightforward. This study outlines a novel strategy for the preparation of elongated nanocapsules, wherein elongated liposomes are deployed as hollow templates. Initially, ciprofloxacin drug nanocrystals were utilized to facilitate the formation of elongated liposomes, followed by adsorption of reversible addition-fragmentation chain transfer (RAFT) oligomers. Subsequent chain-extension polymerization furnished the desired elongated nanocapsule morphology. This proof-of-concept study contributes towards the goal of elongated nanocapsule synthesis, a morphology which can impart improved circulation times in the field of drug delivery.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3252-3267"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566516","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
Mixed dry reverse micelles: potential carriers for oral protein delivery via SEDDS. 混合干反胶束:经SEDDS口服蛋白质递送的潜在载体。
IF 5.5 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-09-01 Epub Date: 2025-02-18 DOI: 10.1007/s13346-025-01810-2
Fabrizio Ricci, Sera Lindner, Simona Summonte, René Holm, Dajun Sun, Nathaniel Washburn, Cecilia Bohns Michalowski, Giustino Di Pretoro, Andreas Bernkop-Schnürch
{"title":"Mixed dry reverse micelles: potential carriers for oral protein delivery via SEDDS.","authors":"Fabrizio Ricci, Sera Lindner, Simona Summonte, René Holm, Dajun Sun, Nathaniel Washburn, Cecilia Bohns Michalowski, Giustino Di Pretoro, Andreas Bernkop-Schnürch","doi":"10.1007/s13346-025-01810-2","DOIUrl":"10.1007/s13346-025-01810-2","url":null,"abstract":"<p><p>The aim of this study was to evaluate the potential of mixed dry reverse micelles (dRMs) to increase the lipophilicity of therapeutic proteins and allow their incorporation into self-emulsifying drug delivery systems (SEDDS). Horseradish peroxidase (HRP) was incorporated in mixed dRMs, forming HRP-dRMs, using soybean phosphatidylcholine (SPC) and sodium docusate (SD) as surfactants. HRP-dRMs were characterized with respect to their distribution coefficient and stability in simulated physiological fluids. Moreover, HRP-dRMs were loaded in SEDDS, which were characterized for their payload, stability, distribution coefficients between the lipophilic phase of SEDDS and release medium and their ability to protect the incorporated protein towards enzymatic degradation in aqueous media containing trypsin and chymotrypsin. The synergistic effect of two surfactants to form dRMs led to a payload of 3% (w/v) for the model protein in a lipophilic phase without the use of organic cosolvents. Moreover, the HRP-dRMs incorporation increased the LogD <sub>n-octanol/water</sub> value of HRP from - 3.36 to 3.10. This increment in lipophilicity provided a higher retention of the protein within the oily droplets, and correled with enzymatic degradation studies, where > 95% of the incorporated protein remained intact. This study provided first evidence for unprecedented amount of a model protein of high molecular weight loaded in SEDDS through dRMs incorporation as a possible tool for their oral delivery, with a 15-fold increment compared to the previously achieved results.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3307-3320"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448531","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
Microfluidic fabrication of pectin-coated liposomes for drug delivery. 用于给药的果胶包被脂质体的微流体制备。
IF 5.5 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-09-01 Epub Date: 2025-02-22 DOI: 10.1007/s13346-025-01812-0
Anitta Lutta, Qian Liu, Gabriel Kristian Pedersen, Mingdong Dong, Holger Grohganz, Line Hagner Nielsen, Signe Tandrup Schmidt
{"title":"Microfluidic fabrication of pectin-coated liposomes for drug delivery.","authors":"Anitta Lutta, Qian Liu, Gabriel Kristian Pedersen, Mingdong Dong, Holger Grohganz, Line Hagner Nielsen, Signe Tandrup Schmidt","doi":"10.1007/s13346-025-01812-0","DOIUrl":"10.1007/s13346-025-01812-0","url":null,"abstract":"<p><p>Polymer coating of nanoparticulate drug delivery systems may enhance the efficacy of oral delivery. Cationic liposomes were coated with pectin biopolymers using microfluidics, with systematic variation of process parameters to optimize pectin-coated liposome fabrication. A pectin/liposome weight ratio of 0.7 and a microfluidic flow rate ratio of 2:1 pectin:liposome were found to be optimal. The resulting formulations displayed particle sizes at least threefold the size of uncoated liposomes, while the surface charge shifted to a highly negative value, indicating full pectin coating of the particles. Further microscopic characterization of the pectin-coated liposomes revealed that the pectins formed a polymeric network within which the liposomes were dispersed or attached. Stability studies revealed that pectin-coated liposomes remained stable during storage, with no displacement of the coating. We determined that microfluidics is a robust method for preparing pectin-coated liposomes, despite the structural differences between the pectins, geometry of the microchip used, and pectin/liposome concentration. Ultimately, the use of microfluidics in formulation development could be highly beneficial, as the process parameters can be easily modified and the process is easily scalable and inexpensive. Additionally, pectins can offer protective properties to the liposomes particularly during oral drug delivery.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2941-2950"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476348","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
Bridging membrane fluidity studies with a predictive model of drug encapsulation to address industrial challenges of liposomal injectables manufacturing. 连接膜流动性研究与药物包封的预测模型,以解决脂质体注射剂制造的工业挑战。
IF 5.5 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-09-01 Epub Date: 2025-02-15 DOI: 10.1007/s13346-025-01807-x
Mariana Biscaia-Caleiras, Nuno Fonseca, Ana Sofia Lourenço, António Nunes, Abel Ferreira, João Nuno Moreira, Sérgio Simões
{"title":"Bridging membrane fluidity studies with a predictive model of drug encapsulation to address industrial challenges of liposomal injectables manufacturing.","authors":"Mariana Biscaia-Caleiras, Nuno Fonseca, Ana Sofia Lourenço, António Nunes, Abel Ferreira, João Nuno Moreira, Sérgio Simões","doi":"10.1007/s13346-025-01807-x","DOIUrl":"10.1007/s13346-025-01807-x","url":null,"abstract":"<p><p>Industrial manufacturing of liposomal drugs, often involves high-temperature processes, resulting in increased energy consumption, prolonged process times, and elevated costs, while posing risks of phospholipid and drug degradation. The current study addresses these challenges by exploring remote loading of doxorubicin into liposomes, at temperatures below the phase transition temperature (PTT) of the primary phospholipid (DSPC, 55 °C). Drug loading efficiencies exceeding 90% at 45 °C were achieved, while efficiencies dropped significantly (6-fold and 23-fold) at 37 °C and 25 °C, respectively. This prompted the hypothesis that efficient drug loading might be attained below the PTT, when a minimal threshold for liposomal membrane fluidity is overcome. Using design of experiments (DoE), key factors influencing fluidity were identified: temperature, cholesterol content and surface tension (dependent on the isotonic agent). A full factorial DoE confirmed that membrane fluidity increased with lower surface tension, and high cholesterol content. A predictive model was also generated establishing a correlation between drug loading efficiency, membrane fluidity, and drug partitioning coefficient (logP). This model revealed that doxorubicin (logP = 1.5) requires a fluidity threshold of 4.41 for efficient loading (≥ 90%), whereas daunorubicin (logP = 2.32) needs a lower threshold of 3.85, suggesting that drugs with higher logP values demand lower fluidity thresholds for effective loading. The model's applicability was validated across various lipid formulations, enabling effective drug loading at temperatures as low as 25 °C, potentially reducing degradation risks and energy costs. Overall, these findings highlight the relevance of liposomal membrane fluidity studies as a potential tool for enabling more effective industrial processes.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3281-3295"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425111","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
Platelet membrane-modified exosomes targeting plaques to activate autophagy in vascular smooth muscle cells for atherosclerotic therapy. 靶向斑块激活血管平滑肌细胞自噬的血小板膜修饰外泌体用于动脉粥样硬化治疗。
IF 5.5 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-09-01 Epub Date: 2025-01-28 DOI: 10.1007/s13346-025-01792-1
Yu Jiang, Zhi-Yao Wei, Zhi-Feng Song, Miao Yu, Ji Huang, Hai-Yan Qian
{"title":"Platelet membrane-modified exosomes targeting plaques to activate autophagy in vascular smooth muscle cells for atherosclerotic therapy.","authors":"Yu Jiang, Zhi-Yao Wei, Zhi-Feng Song, Miao Yu, Ji Huang, Hai-Yan Qian","doi":"10.1007/s13346-025-01792-1","DOIUrl":"10.1007/s13346-025-01792-1","url":null,"abstract":"<p><p>Atherosclerosis is one of the leading causes of ischemic cardiovascular disease worldwide. Recent studies indicated that vascular smooth muscle cells (VSMCs) play an indispensable role in the progression of atherosclerosis. Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated promising clinical applications in the treatment of atherosclerosis. However, there are still challenges and limitations persist in targeted therapy. This study aims to develop a bionic nano-delivery system by fusing platelet membranes with exosomes (MSC-Exo<sup>P</sup>) and explore the anti-atherosclerosis effect of MSC-Exo<sup>P</sup> by improving the targeting efficiency and participating in regulating the pathophysiological processes associated with VSMCs. The morphology, particle size, stability, and fusion efficiency of MSC-Exo<sup>P</sup> were assessed using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), immunofluorescence staining, and Western blotting, respectively. MSC-Exo<sup>P</sup> was administered intravenously into ApoE<sup>-/-</sup> mice via the tail vein. In vivo, immunofluorescence staining was used to assess the targeting efficacy of MSC-Exo<sup>P</sup>. The ORO staining, H&E staining, Masson staining, aortic root immunofluorescence staining, and Western blot were utilized to evaluate the VSMC autophagy and anti-atherosclerosis effects of MSC-Exo<sup>P</sup>. In vitro, the autophagy activation of MSC-Exo<sup>P</sup> on VSMCs was further assessed by immunofluorescence staining and Western blotting. The effects of MSC-Exo<sup>P</sup> on VSMCs proliferation, migration, and foam cell formation were detected by EdU experiment, Transwell experiment, wound healing experiment, ORO staining, and BODIPY staining. The TEM revealed that MSC-Exo<sup>P</sup> retained a ring nanostructure, which was similar to MSC-Exo in morphology. NTA analysis indicated the MSC-Exo<sup>P</sup> exhibited a slight increase after cell membrane fusion. Besides, the stability analysis of exosomes and MSC-Exo<sup>P</sup> resulted in no significant changes in particle size. Western blot analysis confirmed that MSC-Exo<sup>P</sup> simultaneously expressed platelet-specific markers (GPVI, GPIbα, CD62P) and exosome-specific markers (CD81, TSG101, and Alix). In ApoE<sup>-/-</sup> mice, the immunofluorescence of aorta and its roots was significantly enhanced after injection of DiI-labeled MSC-Exo<sup>P</sup>, indicating enhanced targeting of MSC-Exo to atherosclerotic plaques by platelets. In vivo experiments demonstrated that MSC-Exo<sup>P</sup> could significantly suppress the progression of atherosclerosis and reduce the area of atherosclerotic plaques by reducing lipid deposition and necrotic nucleus area and increasing collagen content. In vitro experiments further revealed that the uptake of MSC-Exo<sup>P</sup> by foam cells significantly increased, and their proliferation, migration, and foam formation were inhibited by autophagy activat","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3098-3118"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051975","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
Sex-specific formulations of doxazosin mesylate via direct powder extrusion 3D printing. 甲磺酸多沙唑嗪性别特异性配方通过直接粉末挤出3D打印。
IF 5.5 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-09-01 Epub Date: 2025-04-22 DOI: 10.1007/s13346-025-01862-4
Patricija Januskaite, Alvaro Goyanes, Mine Orlu, Abdul W Basit
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