Drug Delivery and Translational Research最新文献

{"title":"Optimized intranasal delivery of segesterone acetate progestin to the brain using nanoemulsions and microemulsions.","authors":"Carina Peres, Sara Meirinho, Samille Ferreira da Silva, Izamara Maocha, Anabela Chiangalala, Susana Alves Ferreira, Márcio Rodrigues, Shimin Zhang, Narender Kumar, Regine Sitruk-Ware, Rui Caetano Oliveira, Carlos Gaspar, Ana Palmeira-de-Oliveira, Rita Palmeira-de-Oliveira, Gilberto Alves, Graça Baltazar, Adriana O Santos","doi":"10.1007/s13346-025-01897-7","DOIUrl":"https://doi.org/10.1007/s13346-025-01897-7","url":null,"abstract":"","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324760","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":"Advances in constructing biocompatible nanocarriers.","authors":"Xuehui Duan, Xinlei Chu, Yan Du, Yixuan Tang","doi":"10.1007/s13346-025-01893-x","DOIUrl":"https://doi.org/10.1007/s13346-025-01893-x","url":null,"abstract":"<p><p>The design of effective drug nanocarriers requires the prevention of adverse biological interactions such as immune activation and cytotoxicity, making superior biocompatibility a critical determinant for clinical success. While existing reviews predominantly focus on the therapeutic applications of nanomedicines, systematic analyses of biocompatibility optimization strategies remain scarce. To address this gap, we present a review of three primary approaches for constructing biocompatible nanocarriers: (1) inert-material-based frameworks, (2) polymer surface engineering techniques, and (3) biomimetic functionalization methodologies. By evaluating the structural designs and biological mechanisms of commonly employed materials, we elucidated how these strategies leverage inherent material properties and biological interaction principles to regulate biocompatibility. Furthermore, we analyzed the advantages and limitations of each approach, offering guidance for selecting the optimal biocompatibility enhancement methods. This work not only synthesizes current advancements in biocompatible nanocarrier development but also provides actionable insights to advance nanomedicine research and clinical translation.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324758","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":"Micro-needle jet injection technology for tunable drug dispersion at delivery.","authors":"Luoxin Long, Chen Zhang, Hong Hu, Xinjin Zhou, Yuji Wang, Lindsey F Mao, Gengshen Song, Shiyou Li, Shanhong Mao","doi":"10.1007/s13346-025-01901-0","DOIUrl":"https://doi.org/10.1007/s13346-025-01901-0","url":null,"abstract":"<p><p>Extravascular injection represents the predominant modality for contemporary drug administration. Needle injection (NI), a 180-year-old technology, provides a low-cost and effective method for delivering small-molecule drugs. However, it often results in low bioavailability for biomacromolecular drugs. Recently, needle-free jet injection (NFJI) technology has shown promise in enhancing bioavailability by promoting greater drug dispersion at delivery. However, application of the technology in clinical settings impeded by its limitations in tunability and controllability of the initial dispersion. To better understand drug dispersion at delivery, Initial Dispersion Rate (IDR) as a quantitative metric was introduced in this work. Computational Fluid Dynamics (CFD), alongside an in vitro nanosponge-gel model, were employed to investigate the correlation between IDR and various fluid properties and injection parameters. The impact of IDR on pharmacokinetics of biomacromolecular drugs was revealed in the study. Guided by a comprehensive study of IDR, a novel micro-needle jet injection (MNJI) technology was developed. In vivo animal studies demonstrated that MNJI could achieve superior injection efficiency and controllable dispersion compared to NFJI and NI. Furthermore, modifying MNJI configurations enabled tunable IDR, thereby achieving desired bioavailability for biomacromolecular drugs. To the best of our knowledge, IDR was introduced for the first time as a quantitative metric to evaluate extravascular injection efficiency, while MNJI was the first extravascular drug delivery technology that could achieve controllable and tunable dispersion at delivery.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324759","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":"Immunostimulatory effects of IL-12 targeted pH-responsive nanoparticles in macrophage-enriched 3D immuno-spheroids in vitro model.","authors":"Maria José Silveira, Cláudia Martins, Ana P Cardoso, Marc J K Ankone, Rhianna R R Blyth, Maria José Oliveira, Bruno Sarmento, Jai Prakash","doi":"10.1007/s13346-025-01896-8","DOIUrl":"https://doi.org/10.1007/s13346-025-01896-8","url":null,"abstract":"<p><p>Metastatic colorectal cancer (CRC) has the dismal 5-year survival rate of only 14%, and immunotherapies fail to improve the patient outcome. One reason for the poor response rate is the slightly acidic (~ 6.5) immunosuppressive microenvironment. Interleukin 12 (IL-12) is a highly potent pro-inflammatory cytokine that can stimulate tumor immune cells and reverse immunosuppression by inducing interferon gamma (IFN-γ) expression. However, its clinical applications are hindered by systemic side effects. In this study, we developed pH-responsive polymeric nanoparticles (NPs) encapsulating IL-12 to enhance its therapeutic efficacy into the tumor microenvironment (TME). IL-12-loaded pH-responsive NPs induced antitumoral pro-inflammatory response in macrophages at pH ~ 6.5, determined by increased IFN-γ levels and nitric oxide (NO) release, without affecting metabolic activity. In contrast, IL-12-loaded pH non-responsive PLGA NPs showed much lower macrophage activation. To validate the specificity and efficacy in a complex immune-rich microenvironment, we developed a novel CRC 3D immuno-spheroid by incorporating human monocyte-derived macrophages with tumor cells in collagen, mimicking CRC spatial organization and extracellular matrix. The interaction of IL-12 pH-responsive NPs induced macrophage polarization, by providing a reduction of M2-like markers (CD14 + CD163+) while increasing pro-inflammatory M1-like counterparts (CD14 + CD86+). Moreover, IL-12 pH-responsive NPs increased IFN-γ levels and reduced anti-inflammatory IL-10 secretion. Overall, this study provides two major findings (1) a pH-responsive NP system to effectively deliver IL-12 to the TME and reprogram local macrophages into pro-inflammatory phenotype; (2) a macrophage-enriched human 3D immuno-spheroid in vitro system as a tool to test the effectivity of immunomodulatory NPs.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309644","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":"D-mannose augments targeted radioligand-immunotherapy of prostate cancer by enhancing radiosensitivity and reshaping immune microenvironment.","authors":"Lei Tao, Bin Xu, Juan Sun, Jiangtao Yang, Fenghua Meng, Zhiyuan Zhong","doi":"10.1007/s13346-025-01886-w","DOIUrl":"https://doi.org/10.1007/s13346-025-01886-w","url":null,"abstract":"<p><p>Targeted radioligand therapy (TRT) is an emerging therapeutic modality for advanced tumors like metastatic castration-resistant prostate cancer. The patients bare, however, varying degrees of resistance to TRT, which would greatly lessen the treatment efficacy and response rate. Here, we find that oral medication of D-mannose effectively enhances the radiosensitivity of PSMA-positive murine RM1-hPSMA prostate cancer cells to TRT by suppressing glucose metabolism. This metabolic disruption not only impeded the proliferation of RM1-hPSMA cells but also augmented DNA damage within tumor cells subjected to TRT, co-promoting cell apoptosis. Interestingly, TRT-D-mannose combination strongly boosted the anti-tumor immune responses by inducing immunogenic cell death, disrupting the immune evasion mechanisms employed by tumor cells, and reducing immunosuppressive cells in the tumor. D-mannose significantly improved the TRT efficacy for highly aggressive murine RM1-hPSMA and human LNCaP Clone FGC models, without causing adverse effects. Hence, D-mannose is potentially a safe radio-sensitizer and a potent immune activator for TRT.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293516","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":"Crossing the blood-brain barrier: nanoparticle-based strategies for neurodegenerative disease therapy.","authors":"Elena Haro-Martínez, Elena Muscolino, Núria Moral, Jordi Duran, Cristina Fornaguera","doi":"10.1007/s13346-025-01887-9","DOIUrl":"https://doi.org/10.1007/s13346-025-01887-9","url":null,"abstract":"<p><p>Neurodegenerative conditions, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease, represent a critical medical challenge due to their increasing prevalence, severe consequences, and absence of curative treatments. Beyond the need for a deeper understanding of the fundamental mechanisms underlying neurodegeneration, the development of effective treatments is hindered by the blood-brain barrier, which poses a major obstacle to delivering therapeutic agents to the central nervous system. This review provides a comprehensive analysis of the current landscape of nanoparticle-based strategies to overcome the blood-brain barrier and enhance drug delivery for the treatment of neurodegenerative diseases. The nanocarriers reviewed in this work encompass a diverse array of nanoparticles, including polymeric nanoparticles (e.g. micelles and dendrimers), inorganic nanoparticles (e.g. superparamagentic iron oxide nanoparticles, mesoporous silica nanoparticles, gold nanoparticles, selenium and cerium oxide nanoparticles), lipid nanoparticles (e.g. liposomes, solid lipid nanoparticles, nanoemulsions), as well as quantum dots, protein nanoparticles, and hybrid nanocarriers. By examining recent advancements and highlighting future research directions, we aim to shed light on the promising role of nanomedicine in addressing the unmet therapeutic needs of these diseases.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293515","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":"Lipid-based nanocarriers for enhanced gentamicin delivery: a comparative study of liquid crystal nanoparticles and liposomes against Escherichia coli biofilms.","authors":"Anam Ahsan, Timothy J Barnes, Nicky Thomas, Santhni Subramaniam, Clive A Prestidge","doi":"10.1007/s13346-025-01890-0","DOIUrl":"https://doi.org/10.1007/s13346-025-01890-0","url":null,"abstract":"<p><p>Conventional antibiotic therapies often fail to eradicate bacterial biofilms due to limited penetration, altered microenvironments, and the presence of persister cells, contributing to persistent and recurrent infections. As a result,the growing threat of antibiotic-resistant bacteria, particularly those forming biofilms, underscores the urgent need for alternative therapeutic strategies. Lipid-based drug delivery systems have emerged as effective nanocarriers for antimicrobials, offering a promising strategy to combat bacterial biofilms due to their biomimetic properties, biocompatibility, and ability to navigate the complex physical, chemical, and biological barriers posed by biofilms. In this study, we compared liquid crystal nanoparticles (LCNPs) and liposomes as delivery systems for gentamicin (GEN) against Escherichia coli (E. coli) (ATCC 25922 and ATCC 35218) in both planktonic and biofilm forms. Transmission electron microscopy analysis confirmed the particle size of GEN-loaded LCNPs (~ 200 nm) and GEN-loaded liposomes (~ 160 nm), with cubic-shaped LCNPs and lipid bilayer-structured liposomes which remained stable over three weeks at 4ºC. Loading GEN into lipid-based nanoparticles resulted in a two-fold reduction in minimum inhibitory concentration values, without significantly altering the minimum bactericidal concentration. Notably, GEN-LCNPs led to a significant fourfold (for E. coli ATCC 25922) and threefold (for E. coli ATCC 35218) reduction in inhibitory concentrations in biofilm states compared to unformulated GEN, achieving a minimum biofilm inhibitory concentration (MBIC) of 50 μg/mL and 100 μg/mL (P < 0.0001), respectively. In contrast, liposomes showed only a twofold reduction in MBIC values (100-150 μg/mL) for both bacterial biofilms. GEN-loaded LCNPs also reduced the E. coli ATCC 25922 colony-forming unit count by 5000-fold and 4000-fold, while liposomes with similar particle size did not significantly improve GEN's antimicrobial activity. Moreover, LCNPs improved GEN efficacy regardless of particle size or Pluronic^® concentration. In conclusion, our findings suggest that GEN-loaded LCNPs demonstrated superior antimicrobial efficacy against E. coli biofilms compared to liposomes, highlighting their potential as effective nanocarriers for combating antibiotic-resistant infections.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274430","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":"Mucosal administration of lipid nanoparticles containing self-amplifying mRNA induces local uptake and expression in a pig model as a potential vaccination platform against STIs.","authors":"Ibe Van de Casteele, Magalie Plovyt, Magdalena Stuchlíková, Michiel Lanssens, Ben Verschueren, Quenten Denon, Paul Van der Meeren, Sean McCafferty, Arlieke Gitsels, Pieter Cornillie, Niek N Sanders, Aster Vandierendonck, Katrien C K Poelaert, Daisy Vanrompay","doi":"10.1007/s13346-025-01877-x","DOIUrl":"https://doi.org/10.1007/s13346-025-01877-x","url":null,"abstract":"<p><p>Mucosal vaccination generates protective immune responses directly at the primary site of STI infection. However, the delivery of nanoparticles is hindered by the mucus barrier at these mucosal surfaces. Due to this interference, research on mucosal administration of self-amplifying (sa)-mRNA encapsulated in lipid nanoparticles (LNP) is currently limited and inconsistent. Some progress has been reported for nasal mRNA vaccination. However, for STIs, protective immune responses are required at the urogenital tract, which is achieved through intravaginal or intranasal administration. Therefore, in this research, we aimed to determine whether an sa-mRNA-LNP reporter vaccine could be effectively administered mucosally, evaluating its potential as a novel platform for STI vaccination. The sa-mRNA luciferase construct was encapsulated in two LNP formulations. In vitro studies demonstrated that these formulations maintained their potency after being sprayed with different sprayers and exposed to different mucus solutions, except for a human cervicovaginal simulant. Next, pigs received 15 µg of the sa-mRNA intravaginally and intranasally through a mucosal spray or injection. The mucosal spray resulted in expression and uptake only at the vaginal mucosa, whereas injection of the formulations resulted in expression at both mucosal sites. However, expression after spraying in the vaginal mucosa disappeared by day 4 post-administration. No differences were observed between both LNP formulations. These findings demonstrate that sa-mRNA can be used for mucosal administration, and expression can be achieved in a more relevant animal model. However, additional research is needed to develop more suitable particles for these complex environments.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265571","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":"Nanoparticle-based approaches for vascular inflammation in managing hypertension: advancing molecular mechanisms and treatment strategies.","authors":"Althaf Umar K P, Anagha R Anil, Sreeja C Nair, Kanthlal S K","doi":"10.1007/s13346-025-01881-1","DOIUrl":"https://doi.org/10.1007/s13346-025-01881-1","url":null,"abstract":"<p><p>Hypertension is a global health challenge associated with significant morbidity and mortality resulting from vascular inflammation and endothelial dysfunction. Chronic hypertension is characterised by endothelial dysfunction, oxidative stress, immune cell recruitment, and cytokine release, all of which exacerbate vascular inflammation. Despite the availability of various antihypertensive therapies, limitations such as drug resistance and suboptimal targeting hinder their efficacy and reveal their side effects. Nanoparticle-based strategies could present innovative solutions by enabling precise drug delivery, minimising off-target effects, and enhancing therapeutic outcomes. Dual-targeting approaches that focus on molecular mechanistic pathways for managing hypertension using nanoparticle-based methods allow targeted modulation of inflammatory pathways as well. This advancement aids in redefining the management of vascular inflammation as a transformative frontier in antihypertensive therapy, addressing the unmet need for targeted, efficient, and patient-tailored treatment strategies. This review outlines the inflammatory pathophysiology underlying vascular hypertension and underscores the necessity of integrating knowledge gaps while inspiring innovative approaches to combat hypertension effectively. It concludes by identifying potential obstacles and solutions to overcome in order to successfully translate such nano-derived therapies into clinical practice applications.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265572","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":"Development of an in-situ forming implant system for levodopa and carbidopa for the treatment of parkinson's disease.","authors":"Deepa D Nakmode, Sadikalmahdi Abdella, Yunmei Song, Sanjay Garg","doi":"10.1007/s13346-025-01892-y","DOIUrl":"https://doi.org/10.1007/s13346-025-01892-y","url":null,"abstract":"<p><p>Long-acting injectables have gained attraction as a system for treating chronic conditions due to their increased efficacy, safety, and patient compliance. Currently, patients with Parkinsons need to administer oral medications multiple times a day which imposes the significant risk of non-compliance. This study aimed to design an in-situ implant-forming system for controlled delivery of levodopa and carbidopa for up to 1 week which will reduce the need for multiple dosing. The combination of poly-lactic-co-glycolic acid (PLGA _50:50) and Eudragit L-100 was used to prepare the implants and the formulation was optimized to achieve a controlled release over 7 days. The optimized formulation containing 26% PLGA and 6% Eudragit L 100 displayed a favorable release profile and injectability with low viscosity. The optimized formulation in vitro release study revealed an initial burst of 34.17% and 37.16% for levodopa and carbidopa in the first 24 h and about 92% and 81% release within 7 days. A good correlation was observed between the in-vitro drug release data and ex-vivo drug release with a correlation coefficient of 0.91 for levodopa and 0.90 for carbidopa. Viscosity analysis showed the Newtonian behavior of the formulation. Syringeability analysis of the formulation showed that the maximum force required for expelling the formulation was 32.98 ± 0.72 N using a 22 G needle. The in-vitro degradation studies revealed 81.89% weight loss of implant in 7 days. The prepared formulation was assessed for in-vivo performance using a convolution modeling technique using a convolve function in R software. The predicted AUC 0-∞ h for the in-situ forming implant was 26505.5 ng/ml with Cmax, 399.3 ng/ml, and Tmax 24 h assuming 100% bioavailability. The results justify that the prepared in-situ implant forming system can be a promising system for the delivery of levodopa and carbidopa for Parkinson's patients.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246944","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}