Drug Delivery and Translational Research最新文献

{"title":"Statistical optimization of chitosan-based synthesis strategies to generate albumin nanoparticles.","authors":"Aitana Martín-Escaño, Claudia Barbuzano, Juan Manuel Rodríguez-Díaz, Edgar Pérez-Herrero","doi":"10.1007/s13346-026-02046-4","DOIUrl":"10.1007/s13346-026-02046-4","url":null,"abstract":"<p><p>Albumin-based nanoparticles (NPs) are typically synthesized by harsh conditions-based methods that limit their application in clinics and can seriously damage the entrapped drug and even their base material. Despite the potential of the use of chitosan (CS) as stabilizing agent by adapting the ionic gelation method or by adding CS as a coating to albumin NPs generated by desolvation, the influential factors of these methods have not yet been studied. In this article, these synthesis approaches have been optimized by a 2-step DoE-based methodology (a screening process with fractional designs plus a response surface methodology using central composite designs). The application of the ion gelation method to produce albumin-based NPs generates sizes from 66 to 1017 nm, PDI (polydispersity index) values of 0.3-0.6 and surface charges (ZP) from neutral to positive (> 20 mV). The fitted models of the responses depend on four factors (albumin and CS concentration, CS pH and CS:albumin mass ratio). On the other hand, the modification of the desolvation method using CS as a stabilizing coating generates 37-1305 nm NPs, with PDI between 0.4 and 0.7 and highly positive ZP (20-40 mV). In this case, the approximate models for the responses depend on four main effects (albumin and CS concentration, pH of CS and albumin:EtOH volume ratio). Furthermore, in this work the best combinations of factors and levels that allow minimizing PDI and obtaining the minimum and maximum expected values for mean size and ZP of NPs were determined for both synthesis methods. Focusing on the minimum possible PDI, the predicted values for the ion gelation- and desolvation-based methods are 0.363 and 0.341, respectively, which are achieved with values of [BSA] (mg/ml), [CS] (mg/ml), CS pH and CS:BSA or BSA:EtOH ratios (mL:mL) of {2.3,1.4,2.2,1:7.3} and {10,0.5,1.8,1:1}, respectively. These optimized conditions yield acceptable size and ZP values for the ion gelation-based (27.7 nm; 16.4 mV) and optimal values for the desolvation-based (146.2 nm; 29.5 mV).</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3381-3404"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206357","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":"A mechanical reprogramming: synergistic tumor microenvironment normalization improves nano-immunotherapy delivery in prostate cancer via multiphysics modeling.","authors":"Fatemeh Mirala, Madjid Soltani","doi":"10.1007/s13346-026-02051-7","DOIUrl":"10.1007/s13346-026-02051-7","url":null,"abstract":"<p><p>There is a poor response of prostate cancer to immunotherapies because of dysfunctions in the tumor microenvironment (TME) characteristics, like abnormal vasculature structure, stiffened stroma, increased interstitial fluid pressure (IFP), and regions of hypoxia. However, the existing computational modelings are unable to tackle this issue, as they are based on two-dimensional (2D) geometry that ignores TME properties (like TME biphasic composition) and interaction between cancer and immune cells. To address this knowledge gap, this paper offers a patient-specific multiphysics model for prostate cancer. The proposed model is based on three-dimensional (3D) geometry obtained from magnetic resonance imaging (MRI) and combines three complementary approaches to normalizing the tumor microenvironment: vascular normalization via anti-angiogenic therapy, stromal normalization via extracellular matrix softening, and immune checkpoint blockade. One important new aspect of this work is that new nanoparticle delivery models have been developed for 20-100 nm nanoparticles (NP) delivering immunotherapy agents. These equations explicitly incorporate interactions between the components of the TME and directly account for mechanical stress induced by tumor growth, enabling mathematical modeling of physical TME changes and their subsequent impact on the dynamics of immune cells (such as cytotoxic T cells (CD8 + T cells), regulatory T cells (Treg), and pro-inflammatory macrophages (M1-like)/anti-inflammatory macrophages (M2-like) and cancer cells. This capability is absent in previous models. The other important novelty is that for the first time in a prostate cancer model, factors for vascular and stromal normalization and immunotherapy have been incorporated in a 3D geometry. The parameters of this model have been optimized based on literature and preclinical trial data related to immunology and tumors. The sensitivity analysis has confirmed that all therapeutic factors, optimized vascular function (functional vessel density increases from 43 to 112 cm²/cm³), reduced stromal solid stress (decrease in shear modulus from 10.4 to 6.1 kPa), as well as a 70% reduction in IFP (from 1471 to 441 Pa), in combination contribute to a 30% increase in accumulation of nanoparticles in the tumor, 60% increase in the ratio of CD8 + /Tregs, a 45% decrease in the ratio of M1/M2 macrophages, a 15% reduction in the tumor hypoxia gradient, and a 40% decrease in the size of the tumor within 50 days. This model can thus provide a clinically applicable tool for predicting the efficacy of nano-immunotherapy in prostate cancer. Experimental confirmation is required to better evaluate NP toxicity.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3420-3438"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156337","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":"Computational study of Durysta^® implant for glaucoma treatment: drug dispersion and aqueous humor flow in the anterior chamber.","authors":"Ajay Kumar, Avula Benerji Babu, Marepally Flarence","doi":"10.1007/s13346-026-02050-8","DOIUrl":"10.1007/s13346-026-02050-8","url":null,"abstract":"<p><p>Glaucoma is a leading cause of irreversible blindness, with current treatment strategies focusing on reducing the intraocular pressure (IOP). The Durysta^® (bimatoprost) intracameral implant offers a sustained-release alternative to conventional eye drops by continuously delivering medication directly into the anterior chamber (AC). This study employs advanced computational modeling using ANSYS Fluent to investigate the interaction between aqueous humor (AH) flow and drug distribution following Durysta^® implantation. Drug transport is modeled using the unsteady convection diffusion equation, and concentration profiles are analyzed at different times: 10 min, 30 min, 1 h, 1 day, 15 days, 30 days, and 60 days. The results show that AH circulation significantly influences by Durysta^® implant, with flow-driven mixing facilitating its distribution across ocular tissues. In the early phase, high concentration zones appear near the implant, while long-term simulations demonstrate sustained and uniform drug distribution throughout the AC. These findings advance the understanding of sustained intraocular drug delivery and establish a computational framework to guide the optimization of future implant designs, aiming to improve therapeutic outcomes in glaucoma management.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3405-3419"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156486","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":"Intranasal nanoemulsion for targeted medication delivery to the brain: a novel approach to treat psychotic disorder.","authors":"Sudishna Das, Manoleena Sarkar, Arnab Bagchi, Sanjib Bahadur","doi":"10.1007/s13346-026-02054-4","DOIUrl":"10.1007/s13346-026-02054-4","url":null,"abstract":"<p><p>The brain is one of the most delicate & protected organs of the human body. The circulation of blood to the brain is secured by the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and cerebrospinal fluid-brain barrier (CBB). These barriers also restrict the distribution of therapeutics to the central nervous system (CNS) for the treatment of any psychotic disorder. Oral & parenteral routes are the main routes for the delivery of anti-psychotics to the brain. Still, associated drawbacks include the stomach's acidic pH, first-pass metabolism, enzymatic degradation, plasma protein binding and finally, the barriers of brain. One of the novel routes for directly targeting the drug to the brain is the intranasal route, which bypasses the BBB. The drug is delivered to the brain via the olfactory & trigeminal nerve regions located in the septum & ceiling of the nasal cavity, reaching the brain more quickly and at higher concentrations than viat the systemic circulation or other tissues. In most cases, nasal doses are 2-10 times less than the oral dose. Nanoemulsions (NE) are bi-phasic dosage forms of two immiscible liquids stabilized by surfactants having a mean droplet size of 100-300 nm. NE is attracting increasing interest in nose-to-brain delivery (N2B) due to its ability to address issues related to drug solubility & drug stability. The smaller droplet size of NE provides a larger surface area, thereby increasing the dissolution rate according to the Noyes-Whitney equation.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3477-3501"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867116","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":"Zonisamide nanodiamonds for brain targeting: A comprehensive study utilising in silico, in vitro, in vivo, and molecular investigation for successful nose-to-brain delivery for epilepsy management.","authors":"Nihal Mohamed Elmahdy Elsayyad, Omar A Elkady, Mohamed M Swidan, Hassan M Rashed, Tamer M Sakr, Amr M Abdelhamid, Mai A Zaafan, Hanan M El-Laithy","doi":"10.1007/s13346-025-01904-x","DOIUrl":"10.1007/s13346-025-01904-x","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) is a stringent barrier that restricts the successful brain delivery of polar neurotherapeutics molecules. One such molecule is Zonisamide (ZNS), a hydrophilic centrally acting anti-epileptic drug. This study aims to overcome the poor ZNS BBB permeability using the nose-to-brain (NTB) carbon-based biocompatible nanodiamonds (ND) delivery system to deliver ZNS directly to the brain, bypassing the BBB, thereby enhancing its efficacy and reducing systemic side effects associated with oral ZNS currently available formulation in clinical practice. Intranasal (IN) ND-ZNS formulations were optimised using an Artificial neuronal network (ANN) and assessed for particle size (PS), zeta potential, loading efficiency (%LE), morphology, and in vitro release. The optimum radiolabelled ND-ZNS complex F1 biodistribution in different organs and its pharmacokinetics were compared to oral and IN-free ZNS in mice. Temporal lobe epilepsy (TLE) model in rats was used to compare the anti-epileptic activity of IN ND-ZNS F1 to IN free ZNS by assessing brain activity, epileptic biomarkers such as (brain neuronal specific enolase (NSE), neurofilament light polypeptide (NEFL), and matrix metallopeptidase-9 (MMP-9)), hippocampal histopathology and the modulatory effect on epigenetic miR-199/SIRT-1 and PVT-1/BDNF pathways. Optimized ND-ZNS complex F1 consists of a ZNS:ND ratio of 1:2 and sonicated for 5 min exhibited the least PS (193.7 ± 19.3 nm), adequate %LE (87.1 ± 9.2%) similar to ANN predictions, with a biphasic in vitro release profile of ZNS, beneficial for both acute and chronic epilepsy treatment. The IN delivery of ND-ZNS complex F1 showed preferential higher in vivo brain uptake with minimal systemic exposure linked with higher brain/blood ratio and significant (p ≤ 0.05) overall enhanced pharmacokinetics expressed by C_max and AUC _(0-120min) when compared to oral and IN free ZNS_. Moreover, the TLE model confirmed the improved anti-epileptic activity of F1 compared to IN-free ZNS regarding brain activity and hippocampal histopathology, significant suppression of serum NSE, NEFL, MMP-9 levels, miR-199/SIRT-1 pathway, and normalization of PVT-1/BDNF pathway. Therefore, ND used in this study could be a novel, promising carrier to target ZNS directly to the brain via the IN route for effective epilepsy management with less drug dosing and the least systemic side effects.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3286-3309"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567289","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":"Dissolving microneedles incorporating kopexil multicomponent crystals for improved transdermal delivery.","authors":"Yuehua Deng, Si Nga Wong, Wing Chi Nico Chan, Xinyue Zhang, Shing Fung Chow","doi":"10.1007/s13346-025-02042-0","DOIUrl":"10.1007/s13346-025-02042-0","url":null,"abstract":"<p><p>Notwithstanding the rapid advancements in microneedle research, the applications of multicomponent crystals (MCCs) within microneedle drug delivery landscape remain largely underexplored. This study aimed at integrating crystal engineering with powder-carrying microneedle technology to overcome the current therapeutic obstacles in androgenetic alopecia (AGA). Kopexil (KPX), a minoxidil analog for AGA treatment, was successfully synthesized into MCCs with benzoic acid (BA) and salicylic acid (SA), yielding KPX-BA·H₂O cocrystal hydrate and KPX-SA·H₂O salt hydrate. The solid-state properties of the resulting MCCs were thoroughly characterized. Single-crystal analysis indicated that MCCs were stabilized by acid-aminopyrimidine heterosynthons. The KPX MCC powders were further formulated into dissolving microneedles (MNs). In vitro membrane diffusion tests demonstrated KPX MCCs encapsulated in MNs achieved a 1.86-fold and a 3.20-fold reduction in the amounts of KPX diffused compared to KPX·H₂O at 4 h. The diffusion of KPX MCCs was positively correlated with their solubilities, following the first-order kinetic model. With the absence of prior reports on KPX MCCs, these findings can inform the broader development of MCCs for APIs that have yet to be explored. The use of pharmaceutically accepted coformers, scalable fabrication methods, predictable release profiles, favorable biocompatibility, and painless self-application microneedle patches collectively offer a viable strategy for the potential clinical translation of this platform for AGA.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":"16 9","pages":"3351-3367"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873377","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":"A novel approach to fat reduction: integrating traditional Chinese medicine with a dissolving MNs.","authors":"Chengzhe Wang, Feifei Liu, Jieqian Ge, Shuang Zhao, Xiaotian Ma, Shuang Yi, Zixiang Ma, Yan Zhao, Jian Zhuang","doi":"10.1007/s13346-026-02056-2","DOIUrl":"10.1007/s13346-026-02056-2","url":null,"abstract":"<p><p>Obesity is not only a direct cause of health problems, but is also closely related to the incidence rate of a variety of noncommunicable diseases. Intervention for obesity requires high self-discipline and compliance from individuals, which often makes weight loss less smooth and prone to rebound. In this study, we prepared a dissolving microneedle (MN) loaded with compound traditional Chinese medicine (TCM). The base material was composed of a mixture of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP), which met the requirements of solubility and sufficient mechanical properties. For the drug, we chose the Huatanqushi formula, which has a clear fat-reducing effect in clinical practice and is food and medicine homology. The results showed that the MN can penetrate the stratum corneum, rapidly release drugs in the dermis of the abdominal wall, alleviate the inflammatory state of local adipose tissue, regulate systemic lipid metabolism, and ultimately achieve weight loss. This MN patch is suitable for busy office workers to use conveniently, avoiding the discomfort of oral medication and the drawbacks of a large dosage and long medication time. It can effectively intervene in obesity with a minimal effect on the body.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3515-3533"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164607","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":"The PSD-95 inhibitor NA-1 is delivered to the brain upon nasal administration with uptake into the olfactory bulb improved by co-administration with the cell-penetrating peptides lowPro and Tat.","authors":"Solveig Elle Schmidt, Gunhild Joensen, Camilla Sandbjerg, Maria Thaysen, Bente Gammelgaard, Katharina Schindowski, Mie Kristensen","doi":"10.1007/s13346-025-01842-8","DOIUrl":"10.1007/s13346-025-01842-8","url":null,"abstract":"<p><p>Ischemic stroke affects millions of people annually with limited treatment options targeting excitotoxicity, a major cause of cognitive impairment. The PSD-95 inhibitor NA-1 has demonstrated neuroprotective potential, but its efficacy via intravenous administration is hindered by broad systemic distribution, reduced brain exposure, and interaction with thrombolytic agents like alteplase. This study explores the potential of nasal administration as an alternative delivery route to enhance brain uptake and reduce systemic off-target effects of NA-1. A porcine primary olfactory model was exploited to evaluate NA-1 permeability and the impact of co-administration with the cell-penetrating peptides Tat, LowPro, and PenShuf. NA-1 alone permeated the model to a greater extent than a similar sized model dextran compound, with PenShuf improving NA-1 permeability but compromising barrier integrity in vitro. In vivo, nasal administration to mice achieved brain uptake of NA-1, particularly in the olfactory bulb, with co-administration of Tat and LowPro enhancing olfactory bulb delivery. Compared to intravenously administered NA-1, nasal delivery resulted in significantly lower off-target tissue distribution. These findings highlight nasal administration as a qualified alternative for NA-1 delivery, with potential to bypass the limitations of intravenous administration and enable concurrent use with alteplase during acute ischemic stroke.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3274-3285"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779228","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":"Translation of pharmaceutical 3D printing to clinical point-of-care and industrial manufacturing.","authors":"Christos I Gioumouxouzis, Georgios K Eleftheriadis, Athanasios S Kyriakidis, Christina Karavasili","doi":"10.1007/s13346-026-02059-z","DOIUrl":"10.1007/s13346-026-02059-z","url":null,"abstract":"<p><p>Three-dimensional printing of medicines is moving from feasibility to practice across hospital point-of-care manufacture, community-pharmacy compounding and industrial production. Recent signals include a point-of-care printed oral solid dosage form that met bioequivalence in healthy adults, automated capsule preparation with embedded checks in pharmacies and the first approved industrial product. These advances suggest that 3D printing can deliver clinically acceptable quality when responsibilities, verification and documentation are in place. This review integrates evidence across all three settings and offers a critical appraisal of what is required for safe adoption. We examine how regulatory responsibilities should be allocated across distributed sites, how non-destructive testing and chemometric models can be validated for small batches and which digital systems are essential for traceability and oversight. We analyse where economics break even compared with conventional compounding and identify use cases where 3D printing is comparatively advantaged, including low-dose titration, paediatric formats and rapid design iteration. We also outline risks that must be managed, including training and competency, cleaning validation, cross-contamination control and pharmacovigilance across networks. Finally, we propose a near-term agenda that includes standardised conduct of point-of-care trials, multi-site cost and quality benchmarking, explicit guidance on recalls and labelling and deeper industrial-clinical partnerships to turn pilots into routine practice.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3026-3039"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124179","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":"Optimized mucus adhesion and penetration of lipid-polymer nanoparticles enables effective nose-to-brain delivery of perillyl alcohol for glioblastoma therapy.","authors":"Edilson Ribeiro de Oliveira Junior, Jonathan Matheus Silva, Mariana Arraes Salomão, Nathalia Correa de Almeida Oliveira, Carla Santos de Freitas, Natália Noronha Ferreira, Natalia Sanchez Moreno, Camila Fernanda Rodero, Daniel Graziani, Valtencir Zucolotto, Sebastião Antônio Mendanha, Eliana Martins Lima","doi":"10.1007/s13346-025-01837-5","DOIUrl":"10.1007/s13346-025-01837-5","url":null,"abstract":"<p><p>The delivery of drugs directly from the nose to the brain has been explored for the treatment of neurological diseases, such as glioblastoma, by overcoming the blood-brain barrier. Nanocarriers have demonstrated outstanding ability to enhance drug bioavailability in the brain, following intranasal administration. However, the performance of these nanosystems may be hindered by inadequate interactions with the nasal mucosa, limiting their effectiveness in reaching the olfactory region, and consequently, the translocation of particles to the brain. Here, we designed hybrid lipid-polymer nanoparticles (LPNP), containing the cationic lipid DOTAP and the triblock copolymer Pluronic^® F127 to combine the mucoadhesiveness and mucus-penetrating properties. Perillyl alcohol (POH), a molecule currently under clinical trials against glioblastoma, via intranasal route, was entrapped in the nanoparticles. LPNP-POH exhibited a balanced profile of mucus adhesion and penetration, suggesting that the formulation may enhance mucosal retention while maintaining effective mucus diffusivity. In vivo evaluations displayed higher translocation of LPNP-POH from the nasal cavity to the brain. LPNP-POH resulted in a 2.5-fold increase in the concentration of perillyl acid (a primary metabolite of POH) in the cerebral tissue compared to the free drug. In vitro assays demonstrated that LPNP-POH increased the cytotoxicity and reduced the tumor growth of U87MG glioma cells. These results highlighted that the engineered formulation, with optimized mucoadhesiveness and mucus penetration properties, improved nose-to-brain delivery of POH, offering a promising potential for glioblastoma therapy.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3258-3273"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709153","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}