Drug Delivery and Translational Research最新文献

{"title":"Conventional and microfluidic methods: Design and optimization of lipid-polymeric hybrid nanoparticles for gene therapy.","authors":"Daniel González-García, Olga Tapia, Carmen Évora, Patricia García-García, Araceli Delgado","doi":"10.1007/s13346-024-01644-4","DOIUrl":"10.1007/s13346-024-01644-4","url":null,"abstract":"<p><p>Gene therapy holds significant promise as a therapeutic approach for addressing a diverse range of diseases through the suppression of overexpressed proteins and the restoration of impaired cell functions. Developing a nanocarrier that can efficiently load and release genetic material into cells remains a challenge. The primary goal of this study is to develop formulations aimed to enhance the therapeutic potential of GapmeRs through technological approaches. To this end, lipid-polymeric hybrid nanoparticles (LPHNPs) with PLGA, DC-cholesterol, and DOPE-mPEG₂₀₀₀ were produced by conventional single-step nanoprecipitation (SSN) and microfluidic (MF) methods. The optimized nanoparticles by SSN have a size of 149.9 ± 18.07 nm, a polydispersity index (PdI) of 0.23 ± 0.02, and a zeta potential of (ZP) of 29.34 ± 2.44 mV, while by MF the size was 179.8 ± 6.3, a PdI of 0.24 ± 0.01, and a ZP of 32.25 ± 1.36 mV. Furthermore, LPHNPs prepared with GapmeR-protamine by both methods exhibit a high encapsulation efficiency of approximately 90%. The encapsulated GapmeR is completely released in 24 h. The LPHNP suspensions are stable for up to 6 h in 10% FBS at pH 5.4 and 7.4. By contrast, LPHNPs remain stable in suspension in 4.5% albumin at pH 7.4 for 24 h. Additionally, LPHNPs were successfully freeze-dried using trehalose in the range of 2.5-5% as cryoprotectant The LPHNPs produced by MF and SSN increase, 6 and 12 fold respectively, GapmeR cell uptake, and both of them reduce by 60-70% expression of Tob1 in 48 h.Our study demonstrates the efficacy of the developed LPHNPs as carriers for oligonucleotide delivery, offering valuable insights for their scale up production from a conventional bulk methodology to a high-throughput microfluidic technology.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"908-924"},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317158","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}

{"title":"Combination therapy using Cel-CSO/Taxol NPs for reversing drug resistance in breast cancer through inhibiting PI3K/AKT/NF-κB/HIF-1α pathway.","authors":"Huahui Zeng, Xiaohu Zeng, Can Wang, Guoqiang Wang, Qikang Tian, Junwei Zhao, Lingzhou Zhao, Ruiqin Li, Ying Luo, Haotian Peng, Zhenqiang Zhang, Xiaofang Li, Xiangxiang Wu","doi":"10.1007/s13346-024-01653-3","DOIUrl":"10.1007/s13346-024-01653-3","url":null,"abstract":"<p><p>The resistance of malignant tumors to multiple drugs is a significant obstacle in cancer treatment and prognosis. Accordingly, we synthesized a celastrol (Cel) prodrug (Cel-CSO) by conjugating chitosan oligosaccharides (CSO) to Cel for reversing Taxol resistance in chemotherapy, followed by self-assembly with Taxol into a novel nanoplatform of Cel-CSO/Taxol nanoparticles (termed NPs). NPs showed a suitable size (about 153 nm), excellent stability and prolonged release of Cel and Taxol in a manner that depended on both pH and time. NPs effectively inhibited the overexpression of multidrug resistance-related protein P-gp, hypoxia inducible factor-1α (HIF-1α), and triggered the MCF-7/Taxol cell apoptosis through inhibiting the PI3K/AKT/NF-κB/HIF-1α pathway. In tumor-bearing mice, NPs exhibited significant curative effects in inducing apoptosis of MCF-7/Taxol tumors which showed a low expression level of P-gp, microtubule-related proteins TUBB3 and Tau. The results indicated that NPs may be a promising strategy to overcome drug resistance caused by P-gp, which improve the antitumor effects in drug-resistant breast cancer.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"992-1010"},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450067","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}

{"title":"Plant-derived extracellular vesicles: a synergetic combination of a drug delivery system and a source of natural bioactive compounds.","authors":"Mattia D Langellotto, Giovanna Rassu, Carla Serri, Sara Demartis, Paolo Giunchedi, Elisabetta Gavini","doi":"10.1007/s13346-024-01698-4","DOIUrl":"10.1007/s13346-024-01698-4","url":null,"abstract":"<p><p>Exosomes are extracellular nanovesicles secreted by all cell types and have been studied to understand and treat many human diseases. Exosomes are involved in numerous physiological and pathological processes, intercellular communication, and the transfer of substances. Over the years, several studies have explored mammalian-derived exosomes for therapeutic and diagnostic uses. Only recently have plant-derived extracellular vesicles (EVs) attracted attention for their ability to overcome many defects associated with using mammalian-derived extracellular vesicles, such as safety and scale-up issues. The ease of large-scale production, low toxicity, low immunogenicity, efficient cellular uptake, high biocompatibility, and high stability of these nanovesicles make them attractive for drug delivery systems. In addition, their native contents of proteins, miRNAs and secondary metabolites could be exploited for pharmaceutical applications in combination with other drugs. The present review intends to provide adequate tools for studying and developing drug delivery systems based on plant-derived EVs. Therefore, indications concerning extraction methods, characterisation, and drug loading will be offered. Their biological composition and content will also be reported. Finally, the current applications of these systems as nanocarriers for pharmacologically active substances will be shown.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"831-845"},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079710","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}

{"title":"3D printed needleless injector based on thermocavitation: analysis of impact and penetration depth in skin phantoms in a repetitive regime.","authors":"Rafael Zaca-Morán, Doris Giovanna Mitre-Martínez, Juan Castillo-Mixcóalt, Placido Zaca-Morán, Rubén Ramos-García, Julio César Ramírez-San-Juan, Carolina Morán-Raya, Juan Pablo Padilla-Martínez","doi":"10.1007/s13346-024-01639-1","DOIUrl":"10.1007/s13346-024-01639-1","url":null,"abstract":"<p><p>A global issue that requires attention is the duality between the shortage of needles for regular vaccination campaigns and the exponential increase in syringe and needle waste from such campaigns, which has been exacerbated by the COVID-19 pandemic. In response to this problem, this study presents a 3D printed needleless injector based on thermocavitation. The work focused on investigating the interaction of the resulting liquid jets with skin phantoms at different concentrations (1-2%), emphasizing their impact and penetration depth in a repetitive regime. The injector was designed and fabricated from a semi-transparent polymer using a high-resolution 3D printer, allowing the ejection of liquid jets with velocities up to ~ 73 m/s. The impact of these jets on skin phantoms was evaluated using a high-speed camera. After 6 consecutive liquid jets (1% concentration), a maximum penetration depth of ~ 2.5 mm was achieved, delivering approximately 4.7 µL. For the highest concentration (2.0%) and the same number of shots, the penetration depth was reduced to ~ 0.6 mm with a delivered volume of ~ 0.7 µL. An important finding of this study is that the liquid jet with the highest pressure does not cause the maximum penetration depth, but is the result of a series of successive shots. In addition, the velocity and shape of the ejected jet are determined by the amount of solution and the meniscus formed inside the injector. These findings advance the development of precise and efficient thermocavitation-based injectors with broad potential applications in medical and pharmaceutical fields.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"874-884"},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236394","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}

{"title":"Delivery of exogenous miR-19b by Wharton's Jelly Mesenchymal Stem Cells attenuates transplanted kidney ischemia/reperfusion injury by regulating cellular metabolism.","authors":"Xiaoqiang Wu, Xuan Wu, Zhiwei Wang, Xiangyong Tian, Chan Zhang, Guanghui Cao, Yue Gu, Tianzhong Yan","doi":"10.1007/s13346-024-01645-3","DOIUrl":"10.1007/s13346-024-01645-3","url":null,"abstract":"<p><p>Renal ischemia-reperfusion injury (IRI) frequently occurs following kidney transplantation, and exosomes derived from umbilical cord mesenchymal stem cells (WJ-MSC-Exos) have shown promise in treating IRI in transplanted kidneys. Our study delved into the potential mechanism of WJ-MSC-Exos in ameliorating IRI in transplanted kidneys, revealing that miR-19b is abundantly present in WJ-MSC-Exos. Both in vivo and in vitro experiments demonstrated that the absence of miR-19b abolished the protective effects of WJ-MSC-Exos against renal IRI. Mechanistically, miR-19b suppressed glycogen synthase kinase-3β (GSK3β) expression, thereby stabilizing PDXK protein through direct binding. Treatment with WJ-MSC-Exos led to reduced PDXK levels and enhanced pyridoxine accumulation, ultimately mitigating IRI in transplanted kidneys and I/R-induced HK2 cell apoptosis. These findings elucidate the underlying mechanism of WJ-MSC-Exos in alleviating IRI in transplanted kidneys, unveiling novel therapeutic targets for post-kidney transplantation IRI and providing a solid theoretical foundation for the clinical application of WJ-MSC-Exos in IRI treatment post-transplantation.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"925-938"},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450068","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}

{"title":"Chitosan-Artesunate nanoparticles: A dual anti-fibrotic and anti-inflammatory strategy for preventing bleb fibrosis post-glaucoma filtration surgery.","authors":"Jingyuan Liu, Shutong Wang, Guangshuang Tan, Boding Tong, Ying Wu, Lusi Zhang, Bing Jiang","doi":"10.1007/s13346-025-01819-7","DOIUrl":"https://doi.org/10.1007/s13346-025-01819-7","url":null,"abstract":"<p><p>Glaucoma filtration surgery (GFS) effectively lowers intraocular pressure in glaucoma patients, but postoperative bleb fibrosis often leads to surgical failure. Artesunate (ART) has demonstrated antifibrotic potential; however, its clinical use is limited by poor solubility and rapid degradation. This study aimed to develop chitosan-ART nanoparticles (CS@ART NPs) to improve ART's therapeutic efficacy in preventing bleb fibrosis. CS@ART NPs were synthesized using an ionic gelation method for chitosan encapsulation. Their characterization, including analyses of morphology, hydrodynamic properties, surface charge, encapsulation efficiency, drug release kinetics, stability, chemical structure, and mucoadhesive interactions, was carried out using various techniques such as TEM, DLS, zeta potential analysis, HPLC, FT-IR, ¹H-NMR, and adhesion assays. The antifibrotic effects were evaluated in a rabbit GFS model through subconjunctival injection. Histological analysis as well as immunohistochemistry for fibrosis markers α-SMA and fibronectin were detected. In vitro studies were conducted using human primary ocular fibroblasts stimulated with TGF-β1 to assess anti-inflammatory and anti-proliferative effects, measured by EdU incorporation, Western blot for signaling pathway components, and cytokine expression. CS@ART NPs exhibited a uniform size distribution (135.73 ± 0.90 nm), stable dispersion, high encapsulation efficiency (86.4%), and sustained drug release. In the GFS model, a single subconjunctival injection of CS@ART significantly reduced collagen deposition, as well as α-SMA and fibronectin expression at the surgical site. In vitro, CS@ART demonstrated superior antifibrotic effects with a significantly lower IC50 for inhibiting fibroblast proliferation compared to ART alone. Mechanically, CS@ART suppressed the Cyclin D1-CDK4/6, TGF-β1/SMAD, and PI3K/Akt signaling pathways. Additionally, CS@ART showed marked anti-inflammatory effects, reducing inflammatory cell infiltration and IL-6 expression. CS@ART NPs play a dual role both alleviate bleb fibrosis and inflammation after GFS as a promising therapeutic strategy for improving surgical outcomes in glaucoma patients.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523024","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}

{"title":"Microneedle-mediated intracochlear injection safely achieves higher perilymphatic dexamethasone concentration than intratympanic delivery in guinea pig.","authors":"François Voruz, Sharon J Feng, Eugénie Breil, Michelle Yu, Daniella R Hammer, Aykut Aksit, Fereshteh Zandkarimi, Elizabeth S Olson, Jeffrey W Kysar, Anil K Lalwani","doi":"10.1007/s13346-025-01821-z","DOIUrl":"https://doi.org/10.1007/s13346-025-01821-z","url":null,"abstract":"<p><p>Intracochlear injection through the round window membrane (RWM) has been proposed to overcome imprecise drug delivery into the inner ear. Using a novel ultrasharp microneedle, we compared the perilymphatic dexamethasone (DEX) concentration achieved after intratympanic vs. intracochlear injection at two different time points and assessed its safety in guinea pigs. For this purpose, DEX sodium phosphate (10 mg/mL) was administered either in the right middle ear space via continuous intratympanic injection or in the right scala tympani of the cochlea with microneedle-mediated injection (1 µL at 1 µL/min) across the RWM. Both groups were evaluated at 1-hour or 3-hour time points. Perilymph from both cochleae was sampled for liquid chromatography-mass spectrometry, and bilateral cochleae were harvested for immunofluorescence. Eighteen guinea pigs were included. The mean DEX concentration was higher in the intracochlear delivery group than in the intratympanic delivery group at 1-hour time point (mean difference 67,863 ng/mL, 95% CI (8,352-127,374 ng/mL), p = 0.03). No difference was found at 3-hour time point. In every animal on both cochleae, no disruption in hair and supportive cells of the organ of Corti and utricle was observed. Significant middle ear inflammation was observed with the intratympanic delivery method compared to intracochlear. In conclusion, microneedle-mediated intracochlear injection achieves higher perilymphatic DEX concentration than the intratympanic route by a factor of 7 while preserving the cochlear architecture and inducing significantly less middle ear inflammation. In this new era of inner ear therapeutics, the potential for translational application is tangible and promising.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499751","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}

{"title":"Mouse mesenchymal stem cell-derived exosomal miR-205-5p modulates LPS-induced macrophage polarization and alleviates lung injury by regulating the USP7/FOXM1 axis.","authors":"Yinglu Feng, Min Tang, Haopeng Li, Shanglong Yao, Bo Li","doi":"10.1007/s13346-025-01813-z","DOIUrl":"https://doi.org/10.1007/s13346-025-01813-z","url":null,"abstract":"<p><p>Exosomal microRNAs produced from mesenchymal stem cells (MSCs) are crucial in the management of acute lung injury (ALI). In this work, mMSCs separated from bone marrow were used to extract exosomes (MSC-Exos). MSC-Exos treatment attenuated pathological changes and scores, and edema in ALI mice. Also, MSC-Exos administration modulated the concentrations of inflammatory factors as well as the macrophage polarization both in vivo and in vitro. Upregulation of miR-205-5p in MSC-Exos regulated the macrophage polarization and the contents of inflammatory factors in animal and cell models. MiR-205-5p targeted USP7, and negatively modulated the expression of USP7. USP7 interacted with FOXM1, and reduced the ubiquitination degradation of FOXM1. MSC-derived exosomal miR-205-5p modulated ubiquitination of FOXM1 by targeting USP7. The ameliorative effect of MSC-Exos on the macrophage polarization and the inflammatory factors release was reversed with the overexpression of USP7 in animal and cell models. Collectively, MSC-derived exosomal miR-205-5p regulated lipopolysaccharide (LPS)-induced macrophage polarization and alleviated lung injury by the USP7/FOXM1 axis, which developed a potential target for the treatment of ALI.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499754","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}

{"title":"Preclinical testing of antiviral siRNA therapeutics delivered in lipid nanoparticles in animal models - a comprehensive review.","authors":"Yusuf M Idres, Adi Idris, Wenqing Gao","doi":"10.1007/s13346-025-01815-x","DOIUrl":"https://doi.org/10.1007/s13346-025-01815-x","url":null,"abstract":"<p><p>The advent of RNA interference (RNAi) technology through the use of short-interfering RNAs (siRNAs) represents a paradigm shift in the fight against viral infections. siRNAs, with their ability to directly target and silence specific posttranscriptional genes, offer a novel mechanism of action distinct from that of traditional pharmacotherapeutics. This review delves into the growing field of siRNA therapeutics against viral infections, highlighting their critical role in contemporary antiviral strategies. Importantly, this review will solely focus on the use of lipid nanoparticles (LNPs) as the ideal antiviral siRNA delivery agent for use in vivo. We discuss the challenges of siRNA delivery and how LNPs have emerged as a pivotal solution to enhance antiviral efficacy. Specifically, this review focuses on work that have preclinically tested LNP formulated siRNA on virus infection animal models. Since the COVID-19 pandemic, we have witnessed a resurgence in the field of RNA-based therapies, including siRNAs against viruses including, SARS-CoV-2. Notably, the critical importance of LNPs as the ideal carrier for precious 'RNA cargo' can no longer be ignored with the advent of mRNA-LNP based COVID-19 vaccines. siRNA-based therapeutics represents an emerging class of anti-infective drugs with a foreseeable future as suitable antiviral agents.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499773","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}

{"title":"Low-intensity pulsed ultrasound enhances delivery of 30 nm Q10 for improving mental and memory disorder in APP/PS1 mice.","authors":"Qi Luo, Xuanjie Ye, Jinan Xu, Zihui Sun, Panpan Wang, Haishu Chen, Tingting Gao, Qiangfeng Deng, Ziwen Wang, Qin Wang, Xiaoxiao Chen, Zhuowen Zhao, Yiqing Wu, Chuang Yang, Wanjia Lyv, Xingzhou Lyv, Ye Li, Hang Zhao, Ke Jiang, Ziqi Gu, Jing Lin, Yu Sun, Tao Tan, Haiyun Xu, Zhiqian Tong","doi":"10.1007/s13346-025-01814-y","DOIUrl":"https://doi.org/10.1007/s13346-025-01814-y","url":null,"abstract":"<p><p>Patients with Alzheimer's disease (AD) often experience mental and memory disorders with poor outcomes. Coenzyme Q10 can degrade formaldehyde (FA) and improve Alzheimer-related symptoms, but its ability to cross the blood-brain barrier (BBB) is limited. This study investigated whether low-intensity pulsed ultrasound (LIPUS) enhances 30 nm Q10 delivery and improve symptoms in AD model mice. Here, 30 nm Q10 was prepared by encapsulating Q10 in liposomes coupled with PEG, creating PEG-Q10@NPs under 30 nm in diameter. Wild-type mice and APPswe/PS1dE9 mice (a familial AD model) received 30 nm Q10 via intraperitoneal injection, or a combination of 30 nm Q10 and LIPUS (50 or 100 100 mW/cm²). Then the mice's anxiety-like and depression-like behaviors and biochemical index were evaluated. We found that the combination therapy of LIPUS at 100 mW/cm² and 30 nm Q10 was more effective in ameliorating psychosis in AD mice than individual treatments with 30 nm Q10. This effectiveness was linked to higher levels of brain Q10, serotonin (5-HT), and dopamine (DA), along with lower levels of FA and plaques. Especially, excessive FA directly inactivated 5-HT and DA in vitro. The enhanced cellular uptake of Q10 and improved BBB permeability facilitated by LIPUS were confirmed in both cultured cells and wild-type mice. Unexpectedly, LIPUS at the different intensity only partially alleviated anxiety and depression symptoms and memory deficits in AD mice. Hence, this combination therapy of LIPUS and 30 nm Q10 is an innovative strategy for ameliorating mental and cognitive disorders in AD.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491343","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}