Drug Delivery and Translational Research最新文献

{"title":"Exploring the impact of various zwitterionic surface modifications on the mucus diffusion and membrane permeability of lipid-based nanocarriers.","authors":"Antonio Spennacchio, Luca Maurice Richter, Daniel Stengel, Martin Hermann, Angela Assunta Lopedota, Antonio Lopalco, Nunzio Denora, Andreas Bernkop-Schnürch","doi":"10.1007/s13346-025-01990-x","DOIUrl":"https://doi.org/10.1007/s13346-025-01990-x","url":null,"abstract":"<p><p>This study investigates the effect of structural differences among six zwitterionic surfactants on the performance of lipid-based nanoemulsions. Nanoemulsions were prepared using a standardized formulation approach to minimize compositional variability, thereby isolating the influence of surfactant type. The headgroups of the zwitterionic surfactants, phosphorylcholine, carnitine, amine oxide, betaine, and sulfobetaine, were evaluated for their impact on key parameters including physical stability, cytotoxicity, mucus diffusion, and cellular uptake within the overall surfactant structure. Results revealed significant variations in nanoemulsion performance depending on the zwitterionic surfactant structure. Formulations containing the surfactant cocamidopropyl hydroxysultaine exhibited moderate cytotoxicity but demonstrated superior diffusion through porcine mucus and enhanced uptake by human cells. In contrast, n-dodecylphosphocholine-based nanoemulsions showed excellent stability across all tested biorelevant media coupled with low cytotoxicity. Lipid-based nanocarriers formulated with lauryldimethylamine oxide combined good stability in biorelevant media with high mucus diffusion and moderate cellular uptake. Lauryl betaine-based systems displayed low hemolytic and moderate cytotoxic activities, but showed limited mucus penetration and cellular uptake. This study elucidates critical differences among various zwitterionic surfactants and highlights their suitability for liquid pharmaceutical formulations in the nanoscale range.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250283","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":"Photothermal and pH-stimuli-responsive mesoporous silica nanoparticles drug delivery system for targeting the tumor cells.","authors":"Qi Chen, Zhengxi Wu, Yingying Ji, Xiaoying Zheng, Chunyan Liu, Chenyu Zhou, Xiaoqian Shan, Jiying Sheng, Qiang Ren, Kuijie Wei","doi":"10.1007/s13346-025-01972-z","DOIUrl":"https://doi.org/10.1007/s13346-025-01972-z","url":null,"abstract":"<p><p>To improve the precision of cancer therapy, multi-stimuli responsiveness and targeted, controllable drug release are essential components. In this study, we designed an intelligent drug delivery system that integrates chemotherapy and photothermal therapy with pH- and photothermal-sensitive controlled drug release capabilities. This system encapsulates CuS nanoparticles and a model drug Metformin (Met) within Mesoporous Silica Nanoparticles (MSN), which are subsequently coated with a thin layer of Polydopamine (PDA) to enhance multiple photothermal conversion functions. Met, widely recognized for its role in treating type 2 diabetes, has been shown to possess anti-tumor properties. Consequently, it was chosen as the model drug encapsulated within the mesoporous silica nanoparticles. Our investigation about the drug release behavior demonstrated that the PDA coating on MSN not only mitigates the initial burst release of metformin but also facilitates sustained, pH- and thermally-responsive release at pH 6.5, achieving a cumulative release of 67.1% by the tenth day. Furthermore, the PDA modification significantly improves the photothermal conversion performance and stability of CuS@MSN. The photothermal conversion efficiency (PCE) of CuS@MSN and CuS@MSN@PDA (CMP) were measured at 42.7% and 59.9%, respectively. Additionally, on the 28th day post-tumor resection, the met@CMP group exhibited an 80% lower tumor recurrence rate compared to the met group alone. This research highlights the substantial potential of intelligent CMP nanoparticles for multi-stimuli responsive, precise chemo-photothermal synergistic therapy in cancer treatment.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250273","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":"Impact of sodium caprate dosed as a mini-tablet or suspension on insulin delivery and mucosa histomorphology.","authors":"Freja Fredholt, Joanne Heade, Jukka Rantanen, Stine Rønholt, Hanne Mørck Nielsen","doi":"10.1007/s13346-025-01977-8","DOIUrl":"https://doi.org/10.1007/s13346-025-01977-8","url":null,"abstract":"","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250263","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":"A virtual factory for topical formulations based on molecular modeling and drug-polymer interaction studies.","authors":"Harshvardhan Modh, Ayça Altay Benetti, Abu Zayed Badruddoza, Jia Yan, Tomasz Panczyk, Jaymin Shah, Giorgia Pastorin, Matthias Gerhard Wacker","doi":"10.1007/s13346-025-01983-w","DOIUrl":"https://doi.org/10.1007/s13346-025-01983-w","url":null,"abstract":"<p><p>Topical drug delivery offers a cost-effective and non-invasive alternative to systemic drug administration but faces challenges due to the skin's barrier properties and the complex rheology of semisolid formulations. This necessitates a deeper understanding of the interplay between formulation components and their impact on drug release and therapeutic efficacy. Emulsifying two-component polymer system, supplied as ready-to-use liquid dispersions of oil and surfactant, is increasingly used to simplify manufacturing processes. However, their interaction with active pharmaceutical ingredients (APIs) can unpredictably alter formulation properties. This study investigates how the model APIs (bupivacaine, lidocaine, and atenolol) influence key formulation properties, such as rheology, drug release, and manufacturing efficiency. A systematic, dose-dependent reduction in viscosity was observed with increasing API concentration, an effect attributed to the disruption of the polymer network via electrostatic interactions. This effect remained consistent across different amine classes and was successfully fitted using an exponential function. While formulation pH did not significantly affect viscosity, lower pH values accelerated drug release, highlighting the interplay between gel microstructure, drug-polymer interactions, and release kinetics within this polymer system. Molecular modeling revealed preferential localization of ionized APIs at the polymer-oil interface, while unionized APIs adsorbed onto the oil surface. Detachment force simulations further quantified these interactions. Ex-vivo skin permeation studies confirmed the influence of viscosity on drug permeation, with lower viscosity gels exhibiting faster permeation rates. Finally, in a novel molecule-to-manufacturing approach, these multi-scale insights were integrated into a \"Virtual Factory\" model. This model successfully predicted the impact of API concentration on manufacturing parameters, offering a valuable tool to optimize equipment selection, process parameters, and energy consumption. This work provides a comprehensive framework for the rational design of topical systems, connecting molecular interactions to final manufacturing outcomes.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225180","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":"Enhancing vaccine stability in transdermal microneedle platforms.","authors":"Suman Pahal, Feifei Huang, Parbeen Singh, Nidhi Sharma, Hoang-Phuc Pham, Thi Bao Tram Tran, Aseno Sakhrie, Hasan Akbaba, Thanh Duc Nguyen","doi":"10.1007/s13346-025-01854-4","DOIUrl":"10.1007/s13346-025-01854-4","url":null,"abstract":"<p><p>Micron-scale needles, so-called microneedles (MNs) offer a minimally invasive, nearly painless, and user-friendly method for effective intradermal immunization. Maintaining the stability of antigens and therapeutics is the primary challenge in producing vaccine or drug-loaded MNs. The manufacturing of MNs patches involves processes at ambient or higher temperatures and various physio-mechanical stresses that can impact the therapeutic efficacy of sensitive biologics or vaccines. Therefore, it is crucial to develop techniques that safeguard vaccines and other biological payloads within MNs. Despite growing research interest in deploying MNs as an efficient tool for delivering vaccines, there is no comprehensive review that integrates the strategies and efforts to preserve the thermostability of vaccine payloads to ensure compatibility with MNs fabrication. The discussion delves into various physical and chemical approaches for stabilizing antigens in vaccine formulations, which are subsequently integrated into the MNs matrix. The primary focus is to comprehensively examine the challenges associated with the translation of thermostable vaccine MNs for clinical applications while considering a safe, cost-effective approach with a regulatory roadmap. The recent cutting-edge advances facilitating flexible and scalable manufacturing of stabilized MNs patches have been emphasized. In conclusion, the ability to stabilize vaccines and therapeutics for MNs applications could bolster the effectiveness, safety and user-compliance for various drugs and vaccines, potentially offering a substantial impact on global public health.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3414-3438"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991855","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":"Therapeutic approaches for targeting the pediatric brain tumor microenvironment.","authors":"Caroline A Stockwell, Morrent Thang, David E Kram, Andrew B Satterlee, Shawn Hingtgen","doi":"10.1007/s13346-025-01839-3","DOIUrl":"10.1007/s13346-025-01839-3","url":null,"abstract":"<p><p>Central nervous system (CNS) tumors are the most frequent solid malignant tumors in pediatric patients and are the leading cause of tumor-related death in children. Treatment for this heterogeneous group of tumors consists of various combinations of safe maximal surgical resection, chemotherapy, and radiation therapy which offer a cure for some children but often cause debilitating adverse late effects in others. While therapies targeting the tumor microenvironment (TME) like immune checkpoint inhibition (ICI) have been successful in treating some cancers, these therapies failed to exhibit treatment efficacy in the majority of pediatric brain tumors in the clinic. Importantly, the pediatric TME is unique and distinct from adult brain tumors and designing therapies to effectively target these tumors requires understanding the unique biology of pediatric brain tumors and the use of translational models that recapitulate the TME. Here we describe the TME of medulloblastoma (MB) and diffuse midline glioma (DMG), specifically diffuse intrinsic pontine glioma (DIPG), and further present the current drug delivery approaches and clinical administration routes targeting the TME in these tumors, including preclinical and clinical studies.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3363-3389"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995745","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":"Micropore visualization and lifetime following microneedle application to skin of differing pigments.","authors":"Valeria Cota, Nicole K Brogden","doi":"10.1007/s13346-025-01817-9","DOIUrl":"10.1007/s13346-025-01817-9","url":null,"abstract":"<p><p>Solid microneedles allow dermal delivery of drugs that cannot otherwise absorb through skin, via creation of epidermal micropores. The time that the micropores remain open (micropore lifetime) directly impacts drug delivery windows, and darker skin types have extended micropore lifetimes. Here we visualized dermal micropores and measured micropore lifetime in subjects with differing skin pigmentation (ClinicalTrials.gov identifier NCT04867733, registered 29th April 2021). Forty-nine subjects completed the study, self-identifying as Asian, Black, Caucasian, Latinx, and Bi-/multi-racial. Using a colorimeter, skin color was objectively measured and subjects were grouped according to dark (n = 13), medium (n = 19), or light (n = 17) skin. Stainless steel microneedles, 800 μm length, were applied to the arm. Impedance measurements confirmed a breach of skin barrier, suggesting adequate micropore formation. Micropore depth immediately post-microneedle application ranged from 70.3 to 106.6 μm across all subjects (n = 98 total measurements), but was not different between skin color groups, P > 0.05. OCT images were used to calculate micropore closure over 48 h. At 24 h there was no difference in % change in micropore depth between groups. By 48 h there was an 18.1% difference in micropore closure between the lightest and darkest skinned groups, P < 0.05. These data were in agreement with impedance-predicted micropore lifetimes. The longer micropore lifetime in darker skin was independent of micropore depth, and future mechanistic studies of physiological processes underlying these observations would contribute to an understudied area in skin of color research. Proof of concept pharmacokinetics studies would also be useful to investigate the full impact of these differences.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3528-3541"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556057","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":"Two-step ultrasonic cavitation controlled delivery of brain exogenous nucleic acids for ischemic stroke using acoustic-cationic-polymeric-nanodroplets.","authors":"Wei Dong, Guihu Wang, Yichao Chai, Wenjuan Li, Shichang Liu, Huasheng Liu, Wenlei Guo, Senyang Li, Xinrui He, Mingxi Wan, Zongfang Li, Yujin Zong","doi":"10.1007/s13346-025-01828-6","DOIUrl":"10.1007/s13346-025-01828-6","url":null,"abstract":"<p><p>Inefficient and low-precision delivery of exogenous nucleic acids (ENA) severely limits gene therapy on ischemic stroke (IS). Two problems need to be urgently addressed to improve the efficacy of gene therapy; first, the blood brain barrier (BBB) should be open to promote the accumulation of ENA or genetic material carriers in the ischemic brain parenchyma, and second, the efficient delivery of ENA into the ischemic cells. Previous studies applied ultrasonic cavitation either for opening BBB or for inducing sonoporation to deliver genetic materials into cells. However, the effectiveness of the two-step ultrasonic cavitation to deliver ENA in the brain remains unclear, let alone the genetic materials to be controllably delivered into the ischemic brain parenchyma of the IS. This study systematically explored the BBB opening and ENA delivery by the two-step ultrasonic cavitation using artificial acoustic-cationic-polymeric-nanodroplets (ACPNs). The results demonstrated that the first focused ultrasound (FUS), set at parameters of 3.3 MPa, 20 Hz, 200 cycles and 5 s, stimulating intravascular ACPNs cavitation effectively opened BBB to allow nonactivated ACPN extravasation and accumulation into the ischemic brain parenchyma. Then, the extravascular ACPNs enhanced the second ultrasonic cavitation that noninvasively and efficiently controlled ENA delivery to the ischemic cells through sonoporation, particularly applying 3.3 MPa, 60 Hz, 200 cycles and 9 s to control FAM-eNA delivery, and 3.6 MPa, 20 Hz, 200 cycles and 7 s for pEGFP-C1 controlled delivery. Overall, the two-step ultrasonic cavitation represented a potential strategy for IS-targeted ENA controlled delivery.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3695-3715"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565961","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":"Effects of beta and gamma radiation sterilization on growth factor-loaded nanoparticles: an innovative approach for osteoarticular disorders treatment.","authors":"Jorge Ordoyo-Pascual, Sandra Ruiz-Alonso, Idoia Gallego, Laura Saenz-Del-Burgo, Jose Luis Pedraz","doi":"10.1007/s13346-025-01829-5","DOIUrl":"10.1007/s13346-025-01829-5","url":null,"abstract":"<p><p>The prevalence of various diseases, including osteoarticular conditions, is increasing as the world's population ages. These disorders lead to degeneration of bones and joints, diminishing the quality of life of the geriatric population and imposing a significant economic burden on healthcare systems. The aim of the present study is to sterilize nanostructured lipid carriers (NLCs) loaded with vascular endothelial growth factor 165 (VEGF165) and platelet-derived growth factorBB (PDGF-BB) without compromising their properties to improve osteoarticular disease prognosis. Therefore, two methods of sterilization using ionizing radiation - beta radiation and gamma radiation - and two different doses - 12 kGy and 25 kGy - were investigated. Subsequently, the study evaluated whether the sterilization process had any effect on the nanoparticles and encapsulated growth factors by assessing their physicochemical properties, toxicity, release profiles and bioactivity. The treatment with 12 kGy of beta radiation successfully sterilized the batch of nanoparticles without inducing any changes in the physicochemical properties. In addition, the release profile of VEGF165 remained unchanged, although a slight decrease was observed in the case of PDGF-BB. The biological activity of the growth factors showed a slight decrease, with the most effective concentrations being 5 ng/mL for VEGF165 and 50 ng/mL for PDGF-BB. Taken together, these findings suggest that the nanoparticles loaded with VEGF165 and PDGF-BB can be successfully sterilized while retaining both their properties and biological activity. These nanoparticles may offer a promising new approach for the treatment of osteoarticular diseases by enhancing vascularization and promoting cellular proliferation in the affected tissue.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3716-3736"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603818","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":"Harnessing the composition of lipid nanoparticles to selectively deliver mRNA to splenic immune cells for anticancer vaccination.","authors":"Mahmoud A Younis, Yusuke Sato, Yaser H A Elewa, Hideyoshi Harashima","doi":"10.1007/s13346-025-01824-w","DOIUrl":"10.1007/s13346-025-01824-w","url":null,"abstract":"<p><p>Herein, we report a design for lipid nanoparticles (LNPs) that specifically delivers mRNA to splenic immune cells post intravenous administration for potential anticancer vaccination applications. A diverse library of ionizable lipids was screened in vivo, in combination with various helper lipids, where the composition of LNPs was tweaked to control their in vivo performance. The biodistribution of the LNPs was then investigated at both organ and sub-organ levels. Subsequently, the LNPs were recruited to deliver an anticancer mRNA-based vaccine to mice. The in vivo tropism of the LNPs was dramatically affected by the chemical structure of the ionizable lipids in question, where a model lipid, CL15H6, was recognized as displaying high affinity for the spleen. Further optimization of the composition of the LNPs enabled highly efficient and spleen-selective mRNA delivery, where the optimized CL15H6 LNPs demonstrated a high capacity for homing to splenic antigen-presenting cells (APCs). Furthermore, loading the LNPs with a low dose of ovalbumin-encoding mRNA (mOVA), as a model antigen, protected the mice against OVA-expressing tumor challenges and suppressed the tumor growth in tumor-bearing mice by ~ 75%, which was superior to the results of a clinically-relevant formulation. The CL15H6 LNPs proved to be biosafe upon either acute dose escalation or repeated administrations. The novel and scalable platform reported herein is promising for clinical translation as a neoantigen vaccine.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3626-3641"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585089","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}