International Journal of Pharmaceutics: X最新文献

{"title":"Crystal engineering optimizes emodin-tetramethylpyrazine combination: From cocrystal design to in vivo anti-colitis efficacy assessment","authors":"Meiru Liu ,&nbsp;Yinru Jiang ,&nbsp;Penghui Yuan ,&nbsp;Shuang Li ,&nbsp;Baoxi Zhang ,&nbsp;Xia Zhou ,&nbsp;Bin Su ,&nbsp;Yifei Xie ,&nbsp;Dezhi Yang ,&nbsp;Linglei Kong ,&nbsp;Li Zhang ,&nbsp;Yang Lv ,&nbsp;Guanhua Du","doi":"10.1016/j.ijpx.2025.100436","DOIUrl":"10.1016/j.ijpx.2025.100436","url":null,"abstract":"<div><div>Emodin (EMO) shows therapeutic promise for ulcerative colitis (UC), yet its clinical utility is hampered by low bioavailability. To rationally overcome this limitation, this study employed cocrystal engineering, strategically selecting tetramethylpyrazine (TMP)—a natural compound from traditional Chinese medicine—as the cocrystal coformer (CCF). The selection of TMP was guided by a systematic CCF screening strategy, incorporating extensive literature analysis of natural compound CCF candidates, computational chemistry methods to predict favorable hydrogen-bonding interactions and interaction sites with EMO, and machine learning assessment of cocrystallization propensity. Utilizing this rational design approach, we successfully synthesized and characterized a novel EMO-TMP cocrystal through comprehensive solid-state characterization techniques. The resulting cocrystal significantly enhanced the aqueous solubility of EMO while preserving its intrinsic bioactivity. Pharmacokinetic studies confirmed that the cocrystal formulation markedly improved the oral bioavailability of EMO. In a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) model, the EMO-TMP cocrystal demonstrated superior efficacy compared to EMO alone, effectively alleviating colitis symptoms and associated pathological markers. This enhanced <em>in vivo</em> efficacy is attributed to the significantly improved systemic exposure achieved through the rationally designed cocrystal. Our findings establish the EMO-TMP cocrystal as a highly promising strategy to surmount the physicochemical barriers of EMO, unlocking its full clinical potential for UC treatment. Critically, this work not only validates TMP as an efficient and safe CCF specifically suited for active pharmaceutical ingredients (APIs) rich in hydrogen-bond donors, but also exemplifies the value of leveraging formulation principles and compatible components inherent in traditional Chinese medicine through advanced crystal engineering approaches.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100436"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516742","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}

{"title":"Pectinase responsive nanoplatform for oral targeted delivery 5-aminosalicylic acid and zinc coordination driven nanozyme in inflammatory bowel disease treatment","authors":"Yiting Lin ,&nbsp;Siqi Fang ,&nbsp;Xinyi Chen ,&nbsp;Xiang Li ,&nbsp;Xinlin Zhao ,&nbsp;Yanwen Wang ,&nbsp;Jing Lu ,&nbsp;Qingdong Ji ,&nbsp;Shuhui Zheng ,&nbsp;Jiafeng Zou ,&nbsp;Chendong Qi ,&nbsp;Feng Gao","doi":"10.1016/j.ijpx.2025.100362","DOIUrl":"10.1016/j.ijpx.2025.100362","url":null,"abstract":"<div><div>Characterized by weight loss, intestinal ulcerations, and diarrhea with blood or mucus, inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic gastrointestinal condition. The rising incidence of IBD is placing pressure on healthcare systems globally. Although the precise etiology remains elusive, the dysregulation between reactive oxygen species (ROS) and hydrogen sulfide (H₂S) is a crucial determinant in the pathogenesis of inflammatory bowel disease (IBD). Though 5-aminosalicylic acid (5-ASA) is effective in the early-stage of IBD, restoring intestinal environmental balance, its use is limited by off-target problem and toxicity. This study introduces a novel oral nano-drug delivery system that improves efficacy and reduces side effects by coordinating 5-ASA with Zn²⁺ to form nanozymes (5-ASA-Zn²⁺, A-Z) and encapsulating them in nanoplatform (A-Z@cHP), which made from chitosan (CS), hyaluronic acid (HA), pectin (PC) and calcium chloride. The nanozymes displayed uniform particle size, stability, and ability to regulate ROS and H₂S. The nanoplatform showed the characteristic of acid resistance, pectinase responsive drug release, low cytotoxicity, and effective targeting <em>via</em> CD44 receptors. In a DSS-induced mouse colitis model, A-Z@cHP significantly improved body weight, disease activity index, colon length, and colonic barrier while reducing inflammation by restoring the balance of ROS and H₂S. Furthermore, the balance restoration of intestinal flora also benefits from the above regulatory effect of nanoparticles. Biosafety evaluations confirmed no significant side effects. In conclusion, this targeted nanoplatform provides a promising new approach for improving the efficacy of 5-ASA against IBD.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100362"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694324","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}

{"title":"Preparation and in vitro property evaluation of NO-HA@ICG self-assembled nanoparticles for gas therapy synergized with phototherapy","authors":"Jiamin Huang ,&nbsp;Jianhu Jia ,&nbsp;Qian Zhang ,&nbsp;Xiaohui Tang ,&nbsp;Qi Shen ,&nbsp;Wenjun Su ,&nbsp;Jing Zhao ,&nbsp;Mei Wang","doi":"10.1016/j.ijpx.2025.100446","DOIUrl":"10.1016/j.ijpx.2025.100446","url":null,"abstract":"<div><div>The synergistic effect of gas therapy and phototherapy is an innovative therapy in the field of cancer treatment with a unique therapeutic mechanism and application characteristics. NO improves the tumor blood vessels and facilitates the drugs to reach the cancer site, and the heat and ROS generated by phototherapy promote the release of NO and synergistically induce cancer cell Apoptosis. In this study, a self-assembled nanoparticle constructed by NO donor and HA was prepared by microfluidic equipment, and ICG was encapsulated in the nanoparticle and evaluated for its phototherapeutic effect and NO release performance. And the results showed that NO-HA@ICG NPs + laser group produced stronger ROS and NO than Free ICG and NO-HA@ICG NPs groups, which had a synergistic effect. The nanoparticle NO is expected to improve the tumor vascularity to facilitate the drug to reach the cancer site, and not only did the heat and ROS released by phototherapy promote the release of NO, but also synergistically induced the apoptosis of cancer cells with NO.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100446"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568585","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}

{"title":"Biomimetic nanotherapy for P. gingivalis-infected oral squamous cell carcinoma: Photothermal therapy and immunoactivation via precise intracellular bacterial elimination","authors":"Zihan Dai ,&nbsp;Qiaoxin Li ,&nbsp;Longxuan Guo ,&nbsp;Kaijing Zhong ,&nbsp;Jing Cheng ,&nbsp;Xiuhong Weng ,&nbsp;Bo Cheng","doi":"10.1016/j.ijpx.2025.100438","DOIUrl":"10.1016/j.ijpx.2025.100438","url":null,"abstract":"<div><div><em>Porphyromonas gingivalis</em> (<em>P. gingivalis</em>) infection in oral squamous cell carcinoma (OSCC) undermines patient responses to standard therapies by driving chemoresistance, tumor progression, and immune suppression. Mounting research evidence—including our staining of clinical OSCC biopsies—confirms intratumoral <em>P. gingivalis</em> colonization and CXCL2 overexpression as risk factors for poor prognosis. Therefore, precisely eliminating tumor-promoting microorganisms and alleviating immune suppression are crucial for improving the treatment efficacy. Inspired by validated observations, we have developed a unique clinically oriented nanoparticle platform (MC-MM@MPDA) that integrated precise intracellular antibiotic delivery, photothermal tumor ablation, photothermal bactericidal and immune activation. Despite growing interest in OSCC photothermal ablation, this platform is the first to utilize the dual anti-tumor and antibacterial functions of photothermal therapy aiming to achieve targeted therapy tailored to <em>P. gingivalis</em>-infected OSCC. Minocycline (MC) was loaded into mesoporous polydopamine (MPDA) nanoparticles and encapsulated with macrophage membranes, enabling selective homing to infected tumor sites and efficient uptake by cancer cells. Subsequently, the nanoplatform utilized photothermal effects to ablate tumor tissue, eliminate intracellular bacteria and induce immunogenic cell death (ICD). pH-triggered antibiotic release eradicated residual bacteria and unleashed bacterial tumor associated antigens. Alongside damage-associated molecular patterns (DAMPs) generated by ICD, these signals reprogrammed the immunosuppressive microenvironment and established a synergistic antitumor network. In <em>P. gingivalis</em> infected OSCC xenograft models, this platform dramatically suppressed tumor growth, cleared pathogen burden, and overcame bacteria-mediated therapy resistance. By leveraging membrane-mimetic targeting, and synergistic photothermal-immunotherapy, MC-MM@MPDA offered a scalable, biocompatible, and readily translatable strategy to address pathogen-driven barriers in OSCC therapy.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100438"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568583","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}

{"title":"CD276-directed supramolecular nanoplatform with pH-triggered gemcitabine release for potent tumor stromal and vascular suppression","authors":"Jiayi Li ,&nbsp;Hao Liu ,&nbsp;Zhijun Li ,&nbsp;Zhihuan Zheng ,&nbsp;Lanzhu Luo ,&nbsp;Liqing Lin ,&nbsp;Jizhen Lin ,&nbsp;Gang Liu ,&nbsp;Xinhua Lin ,&nbsp;Bing Chen","doi":"10.1016/j.ijpx.2025.100452","DOIUrl":"10.1016/j.ijpx.2025.100452","url":null,"abstract":"<div><div>Gemcitabine (Gem) remains a cornerstone chemotherapy for pancreatic ductal adenocarcinoma, but its clinical efficacy is limited by poor pharmacokinetics, dense fibrotic stroma, and hypovascularization. While pH-responsive liposomes can enhance circulation and targeted drug release, their clinical application is hindered by low drug loading capacity and premature leakage of hydrophilic drugs. To address these challenges, we exploited the high and specific expression of CD276 on pancreatic cancer cells, tumor vasculature, and fibroblasts. We engineered a high-specificity and high-affinity anti-CD276 scFv, and developed a novel nanoplatform (Gem@CPL) that integrates pH-responsive and supramolecular assembly strategies with Gem, achieving 4-fold higher drug loading, improved stability, and tumor-specific release. Cellular and animal studies confirmed that Gem@CPL facilitates tumor-specific accumulation and CD276-mediated internalization, resulting in improved intracellular delivery and therapeutic efficacy. Pharmacokinetic analysis revealed a 2.26-fold prolongation of half-life (t₁/₂) and a significant reduction in volume of distribution (Vd) to 0.11-fold compared to free Gem, indicating superior systemic exposure and minimized off-target distribution. Gem@CPL increased anti-tumor activity by 1.77-fold, demonstrating its enhanced efficacy <em>via</em> sustained circulation and targeted delivery. By specifically targeting CD276, this platform minimizes systemic toxicity and potentially improving patient tolerability, offering promising prospects for clinical translation and better outcomes in pancreatic cancer treatment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100452"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568582","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}

{"title":"Plant-derived extracellular vesicles as a natural drug delivery platform for glioblastoma therapy: A dual role in preserving endothelial integrity while modulating the tumor microenvironment","authors":"Lishan Cui ,&nbsp;Giordano Perini ,&nbsp;Antonio Minopoli ,&nbsp;Valentina Palmieri ,&nbsp;Marco De Spirito ,&nbsp;Massimiliano Papi","doi":"10.1016/j.ijpx.2025.100349","DOIUrl":"10.1016/j.ijpx.2025.100349","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most aggressive primary brain tumor, with limited treatment options due to the restrictive blood-brain barrier (BBB) and the heterogeneity of the blood-tumor barrier (BTB). Temozolomide (TMZ), the standard chemotherapy, suffers from poor BBB permeability, rapid degradation, and systemic toxicity. Plant-derived extracellular vesicles (PDEVs) have emerged as promising natural nanocarriers, offering biocompatibility, stability, and the ability to cross biological barriers. This study investigates the use of extracellular vesicles from <em>Citrus limon</em> L. (LDEs) to encapsulate and deliver TMZ (EVs@TMZ) for GBM treatment.</div><div>LDEs were isolated, characterized, and loaded with TMZ via ultrasonication. Encapsulation efficiency, stability, and physicochemical properties were assessed using UV–Vis and FTIR spectroscopy. A 3D BTB model was developed using bioprinted U87 glioblastoma cells in Matrigel, co-cultured with hCMEC/D3 endothelial cells to replicate the tumor microenvironment. Barrier integrity was evaluated through TEER and FITC-dextran assays. Uptake, cytotoxicity, and tumor invasion were assessed in this model, along with oxidative stress and VEGF-A secretion.</div><div>LDEs effectively encapsulated TMZ, enhancing drug stability under physiological conditions. EVs@TMZ crossed the endothelial barrier while preserving barrier integrity and reducing TMZ-induced ROS production. In the 3D glioblastoma model, EVs@TMZ showed strong cytotoxic effects on tumor cells while minimizing endothelial toxicity and oxidative stress. Moreover, VEGF-A secretion was suppressed, disrupting pro-tumorigenic pathways.</div><div>These findings highlight Citrus-derived EVs as biocompatible, efficient carriers for TMZ delivery, offering a promising approach to overcome current challenges in GBM therapy and supporting further development of PDEVs for brain tumor treatment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100349"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489947","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}

{"title":"A novel EGFR-targeted photosensitizer for the theranostics of skin cancer","authors":"Huijuan Li ,&nbsp;Huijun Li ,&nbsp;Shuang Qi ,&nbsp;Xiaohui Tang ,&nbsp;Shiqi Zhao ,&nbsp;Xin Bian ,&nbsp;Baoqing Tian ,&nbsp;Hua Zhang ,&nbsp;Yuchun Wei ,&nbsp;Dianlong Jia ,&nbsp;Xinyue Han ,&nbsp;Qing Fan","doi":"10.1016/j.ijpx.2025.100413","DOIUrl":"10.1016/j.ijpx.2025.100413","url":null,"abstract":"<div><div>The epidermal growth factor receptor (EGFR) is a critical therapeutic target implicated in the pathogenesis and progression of skin cancer, holding significant promise for enhancing precision diagnosis and treatment efficacy. In this study, we developed ICG-Z_EGFR, a novel EGFR-targeting agent engineered through conjugation of the photosensitizer indocyanine green (ICG) to an EGFR-targeted dimeric affibody (Z_EGFR) for the theranostics of EGFR-positive skin cancer. <em>In vitro</em>, ICG-Z_EGFR-mediated photothermal therapy (PTT) induced significant cell death in EGFR-positive A431 cells, while exhibiting minimal effects on EGFR-negative MLE-12 cells. Compared to free ICG, ICG-Z_EGFR enhanced tumor retention, and significantly improved tumor-targeting capability, making it advantageous for identifying EGFR-positive tumor tissues. Furthermore, ICG-Z_EGFR also exhibited excellent photothermal conversion performance <em>in vivo</em>, and effectively suppressed the growth of A431 tumors through thermal ablation. Importantly, ICG-Z_EGFR demonstrated favorable short-term safety profiles during the <em>in vivo</em> treatment assay. In conclusion, the successfully developed ICG-Z_EGFR in this study, as a novel tumor-targeted photosensitizer, innovatively breaks through the limitations of traditional single-modal treatment. This study would open up new perspectives and pathways for integrated clinical diagnosis and treatment of EGFR-positive skin cancer.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100413"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265807","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}

{"title":"An overview of advanced nanocarrier systems for Ibrutinib delivery: overcoming pharmacokinetic barriers and enabling targeted cancer therapy","authors":"Akshay Shetty,&nbsp;Mahesha Keerikkadu,&nbsp;Pragathi Devanand Bangera,&nbsp;Vamshi Krishna Tippavajhala,&nbsp;Mahalaxmi Rathnanand","doi":"10.1016/j.ijpx.2025.100417","DOIUrl":"10.1016/j.ijpx.2025.100417","url":null,"abstract":"<div><div>Ibrutinib (IBR), a covalent inhibitor of Bruton's tyrosine kinase (BTK), has transformed the treatment of B-cell malignancies like chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström's macroglobulinemia. With its clinical success, IBR is faced with enormous challenges like low aqueous solubility, low oral bioavailability, extensive first-pass metabolism, off-target toxicities, and resistance development. Nanotechnology-based drug delivery systems have been reported to be effective solutions for these issues. This review offers a comprehensive and critical examination of new trends in IBR-loaded nanocarriers, including PEGylated liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, nanostructured lipid carriers, and hybrid nanoplatforms. These nanocarriers showed improved drug solubility, prolonged circulation, controlled release, cancer-specific targeting, and reduced systemic toxicity. Emphasis on advanced approaches such as ligand-mediated targeting, stimuli-sensitive release, and co-delivery systems designed to optimize therapeutic effects and avoid resistance mechanisms. Preclinical models demonstrated improved bioavailability, improved tumor accumulation, and improved safety profiles of the IBR nanocarriers. This review covers the translational hurdles, regulatory aspects, and commercial tractability of nanocarrier-mediated inhibition of BTK. In summary, nanotechnology provides a revolutionary pathway for maximizing IBR therapy that could facilitate more efficient, safer, and targeted care for patients with hematologic cancers.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100417"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145323274","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}

{"title":"Boosting buccal drug absorption: Mechanistic insights into bilosome-mediated delivery","authors":"Eleftheria Pantazoglou ,&nbsp;Scarlett Zeiringer ,&nbsp;Matteo Tollemeto ,&nbsp;Nazanin Zanjanizadeh Ezazi ,&nbsp;Zhongyang Zhang ,&nbsp;Leticia Hosta-Rigau ,&nbsp;Jette Jacobsen ,&nbsp;Ramona Jeitler ,&nbsp;Eva Roblegg ,&nbsp;Line Hagner Nielsen","doi":"10.1016/j.ijpx.2025.100444","DOIUrl":"10.1016/j.ijpx.2025.100444","url":null,"abstract":"<div><div>Effective buccal drug delivery is limited by the barrier properties of the mucosa, necessitating innovative systems to enhance permeability without compromising tissue integrity. In this study, bilosomes composed of sodium glycodeoxycholate and phosphatidylcholine were evaluated as a nanoparticulate platform for buccal drug delivery. Their in vitro uptake was investigated using the TR146 buccal cell line. The bilosomes demonstrated stable physicochemical properties and no aggregation. Functional assays indicated that they transiently opened cell-cell junctions, promoting transport across the mucosal barrier while minimizing toxicity. Quartz crystal microbalance with dissipation monitoring confirmed specific interactions with barrier components, supported by observed modulation of desmosomal junctions and cellular uptake. <em>Ex vivo</em> studies using porcine buccal mucosa further showed concentration-dependent distribution. Collectively, these results suggest that bilosomes are a safe and effective platform for enhancing buccal drug absorption.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100444"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516736","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}

{"title":"A blood-brain barrier-penetrating nanoreactor for tumor microenvironment modulation, precise MR imaging and synergistic therapy of glioma","authors":"Peipei Dou ,&nbsp;Liang Chen ,&nbsp;Yiyang Xie ,&nbsp;Wenbei Xu ,&nbsp;Xinran Zhang ,&nbsp;Xiaomei Deng ,&nbsp;Haiqing Xu ,&nbsp;Jingran Li ,&nbsp;Vincent Kawuribi ,&nbsp;Shaohui Zheng ,&nbsp;Kai Xu ,&nbsp;Jing Zhang","doi":"10.1016/j.ijpx.2025.100448","DOIUrl":"10.1016/j.ijpx.2025.100448","url":null,"abstract":"<div><div>Nanomaterials-based theranostic strategy have emerged as innovative techniques for gliomas treatment. However, the existence of blood-brain barrier (BBB) hinders efficient drug delivery to glioma, and the hypoxic condition of tumor microenvironment (TME) significantly reduces therapeutic efficacy. Thus, in this study, we developed a novel reactive oxygen species (ROS)-generating nanoplatform responsive to the TME. This platform utilized mesoporous PtNi nanoparticles (NPs) as carriers, loaded with chelated gadolinium porphyrin (Gd-HMME), to enable combined sonodynamic and chemodynamic therapy under magnetic resonance imaging (MRI) guidance. Employing a transferrin (Tf)-mediated trans-BBB strategy, Tf-PtNi@Gd-HMME-PEG (TPGP) precisely targeted and penetrated glioma tissues, facilitating T1-weighted enhanced imaging of tumor regions. The MRI enhancement signal achieved was 1.64-fold of the control group. Concurrently, the intrinsic acoustic sensitivity and enzyme-like catalytic activity of TPGP produce substantial ROS under ultrasound stimulation. These ROS interact with hydrogen peroxide in the TME to generate toxic free radicals, collectively acting on tumor cells to deliver a dual assault via sonodynamic and chemodynamic mechanisms to effectively inhibit tumor growth and ameliorate the tumor microenvironment. This study underscores the potential of TPGP as a multifunctional nanoplatform for targeted glioma therapy, combining diagnostic imaging with synergistic therapy to overcome the BBB and hypoxic TME.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100448"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568584","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}