Drug Delivery最新文献

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A systematic review of liposomal nanofibrous scaffolds as a drug delivery system: a decade of progress in controlled release and therapeutic efficacy. 脂质体纳米纤维支架作为药物递送系统的系统综述:十年来在控释和治疗效果方面的进展。
IF 6.5 2区 医学
Drug Delivery Pub Date : 2025-12-01 Epub Date: 2024-12-27 DOI: 10.1080/10717544.2024.2445259
Houssam Aaref Abboud, Romána Zelkó, Adrienn Kazsoki
{"title":"A systematic review of liposomal nanofibrous scaffolds as a drug delivery system: a decade of progress in controlled release and therapeutic efficacy.","authors":"Houssam Aaref Abboud, Romána Zelkó, Adrienn Kazsoki","doi":"10.1080/10717544.2024.2445259","DOIUrl":"https://doi.org/10.1080/10717544.2024.2445259","url":null,"abstract":"<p><p>Drug-loaded liposomes incorporated in nanofibrous scaffolds is a promising approach as a multi-unit nanoscale system, which combines the merits of both liposomes and nanofibers (NFs), eliminating the drawback of liposomes' poor stability on the one hand and offering a higher potential of controlled drug release and enhanced therapeutic efficacy on the other hand. The current systematic review, which underwent a rigorous search process in PubMed, Web of Science, Scopus, Embase, and Central (Cochrane) employing (Liposome AND nanofib* AND electrosp*) as search keywords, aims to present the recent studies on using this synergic system for different therapeutic applications. The search was restricted to original, peer-reviewed studies published in English between 2014 and 2024. Of the 309 identified records, only 29 studies met the inclusion criteria. According to the literature, three different methods were identified to fabricate those nanofibrous liposomal scaffolds. The results consistently demonstrated the superiority of this dual system for numerous therapeutic applications in improving the therapy efficacy, enhancing both liposomes and drug stability, and releasing the encapsulated drug in a proper sustained release without significant initial burst release. Merging drug-loaded liposomes with NFs as liposomal nanofibrous scaffolds are a safe and efficient approach to deliver drug molecules and other substances for various pharmaceutical applications, particularly for wound dressing, tissue engineering, cancer therapy, and drug administration <i>via</i> the buccal and sublingual routes. However, further research is warranted to explore the potential of this system in other therapeutic applications.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2445259"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
ADAMTS5-specific gapmer release from an albumin biomolecular assembly and cartilage internalization triggered by ultrasound.
IF 6.5 2区 医学
Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-02-18 DOI: 10.1080/10717544.2025.2464921
Marwa Elkhashab, Goncalo Barreto, Maxime Fauconnier, Yohann Le Bourlout, Laura B Creemers, Heikki J Nieminen, Kenneth A Howard
{"title":"ADAMTS5-specific gapmer release from an albumin biomolecular assembly and cartilage internalization triggered by ultrasound.","authors":"Marwa Elkhashab, Goncalo Barreto, Maxime Fauconnier, Yohann Le Bourlout, Laura B Creemers, Heikki J Nieminen, Kenneth A Howard","doi":"10.1080/10717544.2025.2464921","DOIUrl":"10.1080/10717544.2025.2464921","url":null,"abstract":"<p><strong>Objective: </strong>Antisense oligonucleotides (ASOs) have reached the clinic; however, they lack tissue specificity. Albumin is a plasma-abundant macromolecule that has been shown to accumulate in inflamed tissues. In this work, we have designed a recombinant human albumin (rHA)-based biomolecular assembly incorporating a DNase-resistant phosphorothioate-based complementary oligonucleotide (cODN) and an anti-ADAMTS5 ASO for potential delivery to inflamed sites. Ultrasound (US) was used to trigger ASO release from the assembly and enhance internalization into articular cartilage.</p><p><strong>Methods: </strong>A phosphorothioate cODN was conjugated to rHA through a maleimide cross-linker after which, a therapeutic ADAMTS5-specific gapmer ASO was annealed to the cODN. ASO release was assessed after exposing the biomolecular assembly to different US conditions using an US-actuated medical needle operating at 32.2 kHz. Gene silencing efficiency of US-treated anti-ADAMTS5 ASO was assessed in human primary chondrocytes isolated from osteoarthritic patients. US-mediated ASO penetration into articular cartilage was assessed on <i>ex vivo</i> bovine articular cartilage.</p><p><strong>Results: </strong>ASO release was observed after exposure to US waves in continuous mode conditions that did not compromise ASO gene silencing efficiency in human chondrocytes. Furthermore, US increased ASO internalization into bovine articular cartilage after 30 min of application without detrimental effects on chondrocyte viability.</p><p><strong>Conclusion: </strong>A medical needle driven by continuous US waves at 32.2 kHz has the capability of disassembling a duplex oligonucleotide and enhancing released ASOs internalization into articular cartilage. This work offers the potential delivery and the local triggered release of ASOs at the surface of articular cartilage providing potential benefits for the treatment of diverse cartilage pathologies.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2464921"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448579","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}
引用次数: 0
Peptides rapidly transport antibiotic across the intact tympanic membrane to treat a middle ear infection.
IF 6.5 2区 医学
Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-02-17 DOI: 10.1080/10717544.2025.2463427
Arwa Kurabi, Emily Sereno, Allen F Ryan
{"title":"Peptides rapidly transport antibiotic across the intact tympanic membrane to treat a middle ear infection.","authors":"Arwa Kurabi, Emily Sereno, Allen F Ryan","doi":"10.1080/10717544.2025.2463427","DOIUrl":"10.1080/10717544.2025.2463427","url":null,"abstract":"<p><p>The tympanic membrane (TM) forms an impenetrable barrier to medical therapies for middle ear (ME) diseases like otitis media. By screening a phage-displayed peptide library, we have previously discovered rare peptides that mediate the active transport of cargo across the intact membrane of animals and humans. Since the M13 filamentous bacteriophage on which the peptides are expressed are large (nearly 1 µm in length), this offers the possibility of noninvasively delivering drugs, large drug packages, or gene therapy to the ME. To evaluate this possibility, EDC chemistry was employed to covalently attach amoxicillin, or neomycin molecules to phage bearing a trans-TM peptide, as a model for large drug packages. Eight hours after application of antibiotic-phage to the TM of infected rats, ME bacterial titers were substantially reduced compared to untreated animals. As a control, antibiotic was linked to wild-type phage, not bearing any peptide, and application to the TM did not affect ME bacteria. The results support the ability of rare peptides to actively deliver pharmacologically relevant amounts of drugs through the intact TM and into the ME. Moreover, since bacteriophage engineered to express peptides are viral vectors, the trans-TM peptides could also transport other viral vectors into the ME.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2463427"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440249","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}
引用次数: 0
Impact of nebulizers on nanoparticles-based gene delivery efficiency: in vitro and in vivo comparison of jet and mesh nebulizers using branched-polyethyleneimine.
IF 6.5 2区 医学
Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-02-10 DOI: 10.1080/10717544.2025.2463428
Rosy Ghanem, Xavier Buin, Tanguy Haute, Justine Philippe, Ghalia Kaouane, Lara Leclerc, Maël Guivarch, Tony Le Gall, Jérémie Pourchez, Tristan Montier
{"title":"Impact of nebulizers on nanoparticles-based gene delivery efficiency: <i>in vitro</i> and <i>in vivo</i> comparison of jet and mesh nebulizers using branched-polyethyleneimine.","authors":"Rosy Ghanem, Xavier Buin, Tanguy Haute, Justine Philippe, Ghalia Kaouane, Lara Leclerc, Maël Guivarch, Tony Le Gall, Jérémie Pourchez, Tristan Montier","doi":"10.1080/10717544.2025.2463428","DOIUrl":"10.1080/10717544.2025.2463428","url":null,"abstract":"<p><p>Nanoparticles-based gene delivery has emerged as a promising approach for the treatment of genetic diseases based on efficient delivery systems for therapeutic nucleic acids (NAs) into the target cells. For pulmonary diseases such as cystic fibrosis (CF), chronic obstructive pulmonary diseases (COPD), infectious disease or lung cancer, aerosol delivery is the best choice to locally deliver NAs into the lungs. It is, therefore, important to investigate the effects of nebulization conditions on the efficiency of delivery. To this purpose, the non-viral vector branched polyethyleneimine (b-PEI, 25 kDa) was investigated for plasmid delivery by aerosol. Two types of nebulizers, jet nebulizer and mesh nebulizer, were compared regarding the properties of the nanoparticles (NPs) formed, the efficiency of NAs delivery <i>in vitro</i> and <i>in vivo</i> models and the pulmonary deposition. The results indicate that the mesh nebulizer has a better gene delivery performance than the jet nebulizer in this application. This superiority was demonstrated in terms of size, concentration, distribution of NPs and efficiency of NAs delivery. However, pulmonary deposition appears to be similar regardless of the nebulizer used, and the difference between the two systems lies in the inhalable dose. These results underline the crucial role of nebulization techniques in optimizing aerosol-mediated gene delivery by b-PEI and highlight the potential of mesh nebulizers as promising tools to improved gene therapy. Therefore, the comparison must be performed for each gene therapy formulation to determine the most suitable nebulizer.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2463428"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390107","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}
引用次数: 0
Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaques.
IF 6.5 2区 医学
Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-03-04 DOI: 10.1080/10717544.2025.2460671
Brett D Story, Sangwan Park, Karolina Roszak, Jaeho Shim, Monica Motta, Michelle Ferneding, Kayla M Rudeen, Andrew Blandino, Monica Ardon, Sophie Le, Leandro B C Teixeira, Glenn Yiu, William F Mieler, Sara M Thomasy, Jennifer J Kang-Mieler
{"title":"Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaques.","authors":"Brett D Story, Sangwan Park, Karolina Roszak, Jaeho Shim, Monica Motta, Michelle Ferneding, Kayla M Rudeen, Andrew Blandino, Monica Ardon, Sophie Le, Leandro B C Teixeira, Glenn Yiu, William F Mieler, Sara M Thomasy, Jennifer J Kang-Mieler","doi":"10.1080/10717544.2025.2460671","DOIUrl":"10.1080/10717544.2025.2460671","url":null,"abstract":"<p><p>A clinical need exists for more effective intravitreal (IVT) drug delivery systems (DDS). This study tested the hypothesis that a novel biodegradable, injectable microsphere-hydrogel drug delivery system loaded with aflibercept (aflibercept-DDS) would exhibit long-term safety and biocompatibility in a non-human primate (NHP) model. We generated aflibercept-loaded poly (lactic-co-glycolic acid) microparticles with a modified double emulsion technique then embedded them into a biodegradable, thermo-responsive poly (ethylene glycol)-co-(L-lactic-acid) diacrylate/N-isopropylacrylamide hydrogel. Aflibercept-DDS (50 µL, 15 µg) was injected into the right eye of 23 healthy rhesus macaques. A complete ophthalmic examination, intraocular pressure (IOP), corneal pachymetry, specular microscopy, A-scan biometry, streak retinoscopy, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and electroretinography (ERG) were performed monthly. Globes from 7 NHPs were histologically examined. Aflibercept-DDS was visualized in the vitreous up to 9 months post-IVT injection, slightly impeding fundoscopy in 4 of 23 eyes; no other consistent abnormalities were appreciated during ophthalmic examination. The IOP and total retinal thickness remained normal in all animals over all timepoints. Central corneal thickness, endothelial cell density, axial globe length, and refractive error did not significantly differ from baseline. Scotopic mixed rod-cone implicit times and amplitudes along with photopic cone response implicit times and amplitudes did not significantly differ from control values. No retinal or choroidal vascular abnormalities were detected with FA and normal retinal architecture was preserved using SD-OCT. Intravitreal injection of a biodegradable aflibercept-DDS was safe and well tolerated in NHPs up to 24 months.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2460671"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Exploring the efficacy and constraints of platinum nanoparticles as adjuvant therapy in silicosis management. 探讨纳米铂辅助治疗矽肺的疗效和局限性。
IF 6.5 2区 医学
Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-01-13 DOI: 10.1080/10717544.2024.2445257
Ge Ban, Yuanjie Chen, Yingbing Liang, Xiaona Wang, Dan Ding, Rui Liu, Jingjing Jia, Ran Zhao, Chenxia Wang, Na Li
{"title":"Exploring the efficacy and constraints of platinum nanoparticles as adjuvant therapy in silicosis management.","authors":"Ge Ban, Yuanjie Chen, Yingbing Liang, Xiaona Wang, Dan Ding, Rui Liu, Jingjing Jia, Ran Zhao, Chenxia Wang, Na Li","doi":"10.1080/10717544.2024.2445257","DOIUrl":"10.1080/10717544.2024.2445257","url":null,"abstract":"<p><p>Silicosis represents a formidable occupational lung pathology precipitated by the pulmonary assimilation of respirable crystalline silica particulates. This condition engenders a cascade of cellular oxidative stress via the activation of bioavailable silica, culminating in the generation of reactive oxygen species (ROS). Such oxidative mechanisms lead to irrevocable pulmonary impairment. Contemporary scholarly examinations have underscored the substantial antioxidative efficacy of platinum nanoparticles (PtNPs), postulating their utility as an adjunct therapeutic modality in silicosis management. The physicochemical interaction between PtNPs and silica demonstrates a propensity for adsorption, thereby facilitating the amelioration and subsequent pulmonary clearance of silica aggregates. In addition to their detoxifying attributes, PtNPs exhibit pronounced anti-inflammatory and antioxidative activities, which can neutralize ROS and inhibit macrophage-mediated inflammatory processes. Such attributes are instrumental in attenuating inflammatory responses and forestalling subsequent lung tissue damage. This discourse delineates the interplay between ROS and PtNPs, the pathogenesis of silicosis and its progression to pulmonary fibrosis, and critically evaluates the potential adjunct role of PtNPs in the therapeutic landscape of silicosis, alongside a contemplation of the inherent limitations associated with PtNPs application in this context.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2445257"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970027","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}
引用次数: 0
Ginsenoside compound K-based multifunctional liposomes for the treatment of rheumatoid arthritis.
IF 6.5 2区 医学
Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-02-16 DOI: 10.1080/10717544.2025.2464190
Meng Zhang, Ru Zhang, Chunbo Feng, Xinnan Jiang, Xinchun Xu, Jianxin Wang
{"title":"Ginsenoside compound K-based multifunctional liposomes for the treatment of rheumatoid arthritis.","authors":"Meng Zhang, Ru Zhang, Chunbo Feng, Xinnan Jiang, Xinchun Xu, Jianxin Wang","doi":"10.1080/10717544.2025.2464190","DOIUrl":"10.1080/10717544.2025.2464190","url":null,"abstract":"<p><p>The clinical treatment of rheumatoid arthritis (RA) with first-line therapeutic drugs is hindered by the poor solubility, low bioavailability, off-target toxicity, and insufficient accumulation in inflamed joints. Liposomes have been shown to mitigate some of these limitations in drug delivery systems. However, the use of cholesterol to stabilize liposomal structures remains controversial due to its potential association with cardiovascular diseases. Here, we developed a novel liposome based on ginsenoside compound K (CK), which not only serves as an effective therapeutic agent for RA but also replaces cholesterol as a membrane stabilizer to address these challenges. Compared with conventional liposomes, ginsenoside CK Liposomes (CK@Lipo) are excellent nanoparticles, with CK stabilizing the liposomal structure and providing targeting functionality toward inflamed joints. When encapsulated with dexamethasone (Dex), CK@Lipo exhibits a synergistic anti-inflammatory effect, slowing the progression of RA. This study provides a theoretical basis for the future development of multifunctional novel ginsenoside CK@Lipo.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2464190"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432673","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}
引用次数: 0
Development of a conjunctival contact-type drug delivery device for latanoprost using hyaluronic acid. 利用透明质酸开发拉坦前列腺结膜接触式给药装置。
IF 6.5 2区 医学
Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-02-04 DOI: 10.1080/10717544.2025.2459775
Soomin Lee, Mi-Young Jung, Choul Yong Park
{"title":"Development of a conjunctival contact-type drug delivery device for latanoprost using hyaluronic acid.","authors":"Soomin Lee, Mi-Young Jung, Choul Yong Park","doi":"10.1080/10717544.2025.2459775","DOIUrl":"10.1080/10717544.2025.2459775","url":null,"abstract":"<p><p>Effective topical drug delivery is crucial for glaucoma treatment, necessitating more convenient methods to enhance patient compliance. This study evaluates the efficacy and safety of using freeze-dried hyaluronic acid (HA) as a carrier for a novel conjunctival-contact drug delivery system. We developed HA tablets loaded with latanoprost (HA-latanoprost) and verified the concentration using high-performance liquid chromatography. Twenty mice (C57BL6) were divided into four groups (<i>n</i> = 5 per group): normal saline (group 1), control HA tablet (group 2), Xalatan™ (group 3), and HA-latanoprost tablet (group 4). Treatments were administered to the right eyes, with the left eyes serving as no-treatment controls. Intraocular pressure (IOP) and irritation (measured by scratching motions) were monitored for 10 days. On day 10, we quantified gene expression of inflammatory cytokines and IOP-affecting proteins using polymerase chain reaction, and performed histological and immunohistochemical analyses. Results showed that IOP was significantly lower in groups 3 and 4 compared to the other groups, with group 4 exhibiting the greatest reduction by day 10. Group 4 also experienced less irritation. Additionally, group 4 had lower expression of inflammatory cytokine genes and higher expression of IOP-lowering protein genes compared to group 3. No significant side effects were observed in any group. Overall, HA-latanoprost effectively lowered IOP and reduced ocular irritation more than latanoprost eyedrops in mice. However, these results are based on animal testing, so further development is needed for clinical use.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2459775"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188641","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}
引用次数: 0
Machine learning-assisted design of immunomodulatory lipid nanoparticles for delivery of mRNA to repolarize hyperactivated microglia.
IF 6.5 2区 医学
Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-03-03 DOI: 10.1080/10717544.2025.2465909
Mehrnoosh Rafiei, Akbar Shojaei, Ying Chau
{"title":"Machine learning-assisted design of immunomodulatory lipid nanoparticles for delivery of mRNA to repolarize hyperactivated microglia.","authors":"Mehrnoosh Rafiei, Akbar Shojaei, Ying Chau","doi":"10.1080/10717544.2025.2465909","DOIUrl":"10.1080/10717544.2025.2465909","url":null,"abstract":"<p><p>Regulating inflammatory microglia presents a promising strategy for treating neurodegenerative and autoimmune disorders, yet effective therapeutic agents delivery to these cells remains a challenge. This study investigates modified lipid nanoparticles (LNP) for mRNA delivery to hyperactivated microglia, particularly those with pro-inflammatory characteristics, utilizing supervised machine learning (ML) classifiers. We developed and screened a library of 216 LNP formulations with varying lipid compositions, N/P ratios, and hyaluronic acid (HA) modifications. The transfection efficiency of eGFP mRNA was assessed in the BV-2 murine microglia cell line under different immunological states, including resting and activated conditions (LPS-activated and IL4/IL13-activated). ML-guided morphometric analysis tracked the phenotypes of various microglia subtypes before and after transfection. Four supervised ML classifiers were investigated to predict transfection efficiency and phenotypic changes based on LNP design parameters. The Multi-Layer Perceptron (MLP) neural network emerged as the best-performing model, achieving weighted F1-scores ≥0.8. While it accurately predicted responses from LPS-activated and resting cells, it struggled with IL4/IL13-activated cells. The MLP model was validated by predicting the performance of four unseen LNP formulations delivering eGFP mRNA to LPS-activated BV2 cells. HA-LNP2 emerged as optimal formulation for delivering target IL10 mRNA, effectively suppressing inflammatory phenotypes, evidenced by shifts in cell morphology, increased IL10 expression, and reduced TNF-α levels. We also evaluated HA-LNP2 on LPS-activated human iPSC-derived microglia, confirming its efficacy in modulating inflammatory responses. This study highlights the potential of tailored LNP design and ML techniques to enhance mRNA therapy for neuroinflammatory disorders by leveraging carrier's immunogenic properties to modulate microglial responses.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2465909"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540603","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}
引用次数: 0
Targeted nanoliposomes for precision rheumatoid arthritis therapy: a review on mechanisms and in vivo potential.
IF 6.5 2区 医学
Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-02-01 DOI: 10.1080/10717544.2025.2459772
Rushikesh Girase, Nayan A Gujarathi, Amey Sukhia, Sri Sai Nikitha Kota, Tulshidas S Patil, Abhijeet A Aher, Yogeeta O Agrawal, Shreesh Ojha, Charu Sharma, Sameer N Goyal
{"title":"Targeted nanoliposomes for precision rheumatoid arthritis therapy: a review on mechanisms and <i>in vivo</i> potential.","authors":"Rushikesh Girase, Nayan A Gujarathi, Amey Sukhia, Sri Sai Nikitha Kota, Tulshidas S Patil, Abhijeet A Aher, Yogeeta O Agrawal, Shreesh Ojha, Charu Sharma, Sameer N Goyal","doi":"10.1080/10717544.2025.2459772","DOIUrl":"10.1080/10717544.2025.2459772","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is an inflammatory immune-triggered disease that causes synovitis, cartilage degradation, and joint injury. In nanotechnology, conventional liposomes were extensively investigated for RA. However, they frequently undergo rapid clearance, reducing circulation time and therapeutic efficacy. Additionally, their stability in the bloodstream is often compromised, resulting in premature drug release. The current review explores the potential of targeted liposomal-based nanosystems in the treatment of RA. It highlights the pathophysiology of RA, explores selective targeting sites, and elucidates diverse mechanisms of novel liposomal types and their applications. Furthermore, the targeting strategies of pH-sensitive, flexible, surface-modified, PEGylated, acoustic, ROS-mediated, and biofunctionalized liposomes are addressed. Targeted nanoliposomes showed potential in precisely delivering drugs to CD44, SR-A, FR-β, FLS, and toll-like receptors through the high affinity of ligands. <i>In vitro</i> studies interpreted stable release profiles and improved stability. <i>Ex vivo</i> studies on skin demonstrated that ultradeformable and glycerol-conjugated liposomes enhanced drug penetrability. <i>In vivo</i> experiments for liposomal types in the arthritis rat model depicted remarkable efficacy in reducing joint swelling, pro-inflammatory cytokines, and synovial hyperplasia. In conclusion, these targeted liposomes represented a significant leap forward in drug delivery, offering effective therapeutic options for RA. In the future, integrating these advanced liposomes with artificial intelligence, immunotherapy, and precision medicine holds great promise.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2459772"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074272","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}
引用次数: 0
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