International Journal of Pharmaceutics: X最新文献_第5页

Ionto phoretic delivery of caspofungin acetate to the cornea and sclera and its intracorneal biodistribution 醋酸卡泊真菌素在角膜和巩膜中的离子传递及其在角膜内的生物分布

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-11-19 DOI: 10.1016/j.ijpx.2025.100451

Laura Gisela González Iglesias , Yogeshvar N. Kalia

Caspofungin (CAS) is a potent antifungal agent belonging to the echinocandin family. It is a water-soluble dication at physiological pH, making it a good candidate for iontophoresis. Intracorneal iontophoretic delivery and biodistribution of CAS and its electrically assisted transport into the sclera were investigated as a function of experimental conditions, including donor concentration (1, 5 and 10 mg/mL) and application time (5 and 20 min) using an in-house set-up (with Ag/AgCl electrodes) and a marketed iontophoretic applicator (Iontofor CXL®) that used inert (stainless steel) electrodes. CAS deposition after passive delivery for 20 min (10 mg/mL) was 64.9 ± 23.7 μg/cm² and 370.9 ± 67.49 μg/cm² in the cornea and sclera, respectively. This increased by ∼14- and 3-fold, respectively, after iontophoresis at current densities of 1.5 mA/cm² and 3.5 mA/cm², respectively, for corneal and scleral application using the in-house set-up. The same trends were observed in the Iontofor CXL® studies – although the superiority of iontophoresis over passive delivery was less pronounced due to the electrolysis of water at the anode and the creation of competing hydroxonium ions in the anodal compartment. Intracorneal biodistribution studies showed that after iontophoresis using the Iontofor CXL® (1 mA, 20 min) significantly greater amounts of CAS were present in each lamella as compared to passive delivery and higher CAS concentrations were also achieved in the stroma and endothelium. CAS concentrations in the epithelium, stroma and endothelium after short-duration iontophoresis (1 mA for 5 min) – were > 100-fold higher than the MIC₉₀ reported for Candida albicans and Aspergillus spp.

Caspofungin （CAS）是一种有效的抗真菌药物，属于棘白菌素家族。它在生理pH值下是一种水溶性药物，使其成为离子导入的良好候选者。使用内部装置（Ag/AgCl电极）和使用惰性（不锈钢）电极的市售离子吸入剂（Iontofor CXL®），研究了CAS角膜内离子吸入剂的递送和生物分布及其在巩膜内的电辅助运输作为实验条件的函数，包括供体浓度（1,5和10mg /mL）和应用时间（5和20分钟）。被动给药20 min （10 mg/mL）后，角膜和巩膜的CAS沉积量分别为64.9±23.7 μg/cm2和370.9±67.49 μg/cm2。在使用内部装置分别以1.5 mA/cm2和3.5 mA/cm2的电流密度离子导入角膜和巩膜后，这一数值分别增加了约14倍和3倍。在Iontofor CXL®研究中也观察到了同样的趋势——尽管由于阳极处的电解水和阳极室中竞争性氢氧根离子的产生，离子透入优于被动输送的优势不那么明显。角膜内生物分布研究表明，使用Iontofor CXL®离子导入（1 mA， 20分钟）后，与被动给药相比，每个片层中存在的CAS量显著增加，基质和内皮中也达到了更高的CAS浓度。短时间离子电泳（1 mA 5 min）后，上皮、间质和内皮中的CAS浓度比白色念珠菌和曲霉的MIC90高100倍。

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引用次数: 0

Spray drying: From a traditional technology to modern biotechnological applications 喷雾干燥：从传统技术到现代生物技术的应用

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-11-17 DOI: 10.1016/j.ijpx.2025.100449

Andrea Milanesi , Giada Diana , Alessandro Candiani , Alessandro Sodano , Paolo Rassè , Andrea Foglio Bonda , Elia Bari , Maria Luisa Torre , Lorena Segale , Lorella Giovannelli

Spray drying, first patented in the late 19^th century, has evolved into a versatile technology for converting liquid feeds into stable, free-flowing powders. Its fundamental strength lies in the rapid atomization and solvent evaporation. It enables precise control over particle size, morphology, and moisture content, making it a consolidated tool across food, chemical, and pharmaceutical industries. In the pharmaceutical field, it has been successfully applied to inhalable powders, amorphous solid dispersions, and controlled-release systems. At the same time, innovations in equipment design and Quality by Design strategies have improved robustness and scalability. Emerging applications now highlight its potential to stabilize biopharmaceuticals and vaccines, where dry powder formulations can enhance shelf life and reduce reliance on the cold chain. Similarly, spray drying has become central in nanomedicine through “nano-into-micro” engineering strategies that transform nanoscale carriers into inhalable or targeted dry powders. A further frontier is aseptic spray drying, which addresses sterility requirements for parenteral formulations and vaccines, representing a key step toward industrial adoption. This review outlines the fundamental principles of spray drying, examines the impact of formulation components, and discusses challenges in scale-up and industrial implementation. It then explores the most recent advances in biopharmaceuticals, nanomedicine, and aseptic processing, offering an integrated perspective on how spray drying is transitioning from a traditional drying method into a platform technology for modern biotechnology and pharmaceutical applications.

喷雾干燥在19世纪末首次获得专利，现已发展成为一种将液体饲料转化为稳定、自由流动的粉末的通用技术。它的基本优点在于快速雾化和溶剂蒸发。它可以精确控制颗粒大小，形态和水分含量，使其成为食品，化学和制药行业的综合工具。在制药领域，它已成功地应用于可吸入粉末，无定形固体分散体和控释系统。同时，设备设计和设计质量策略的创新提高了鲁棒性和可扩展性。现在新兴的应用突出了其稳定生物制药和疫苗的潜力，其中干粉配方可以延长保质期并减少对冷链的依赖。类似地，喷雾干燥已经成为纳米医学的核心，通过“纳米到微”的工程策略，将纳米级载体转化为可吸入或靶向干燥粉末。另一个前沿是无菌喷雾干燥，它解决了肠外配方和疫苗的无菌要求，代表了工业采用的关键一步。这篇综述概述了喷雾干燥的基本原理，检查了配方成分的影响，并讨论了扩大规模和工业实施中的挑战。然后探讨了生物制药、纳米医学和无菌加工的最新进展，提供了一个关于喷雾干燥如何从传统干燥方法过渡到现代生物技术和制药应用平台技术的综合视角。

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引用次数: 0

Can therapeutic potency of a cancer nanomedicine be predicted by pain-related behavioral test in subcutaneous tumor model? 皮下肿瘤模型疼痛相关行为测试能否预测纳米肿瘤药物的治疗效果？

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-11-17 DOI: 10.1016/j.ijpx.2025.100450

Ye Tao , Xiaohui Cai , Zhongping Chen

Cancer nanomedicines have shown great potential in fighting against cancer. While the development of cancer nanomedicines is advancing rapidly, preclinical assessment approaches for their therapeutic potency have stagnated. In view of high prevalence of cancer pain in cancer patients, we aim to determine whether therapeutic potency of a cancer nanomedicine can be predicted by pain-related behavioral test in subcutaneous tumor model, the simplest and most widely used tumor model in oncology. Behavioral profiles reveal that subcutaneous tumor, probably irrespective of tumor type, presents with spontaneous pain (open field test) and evoked pain (von Frey test for mechanical allodynia; Hargreaves test, hot plate test, and tail flick test for thermal hyperalgesia; cold plate test and acetone drop test for thermal allodynia). Using doxorubicin (DOX)-loaded lipid nanoparticles (LNPs) (LNPs/DOX) as a representative cancer nanomedicine and ropivacaine (ROP)-loaded LNPs (LNPs/ROP) as a pain nanomedicine, it is validated that inhibiting subcutaneous tumor growth can relieve cancer pain, while delaying the growth cannot, despite a significant difference found compared with non-treatment group. Moreover, behavioral results in all the tests are consistent and von Frey test is suggested the most sensitive among them. It is strongly suggested that pain-related behavioral test can serve as a powerful tool to predict therapeutic potency of a cancer nanomedicine in vivo in treating subcutaneous tumor.

纳米抗癌药物在抗癌方面显示出巨大的潜力。虽然癌症纳米药物的发展正在迅速推进，但对其治疗效力的临床前评估方法却停滞不前。鉴于癌症患者中癌性疼痛的高发性，我们的目的是通过肿瘤模型中最简单、应用最广泛的肿瘤模型——皮下肿瘤模型的疼痛相关行为测试，来确定一种癌症纳米药物的治疗效力是否可以预测。行为特征显示皮下肿瘤，可能与肿瘤类型无关，表现为自发性疼痛（开场试验）和诱发性疼痛（von Frey机械异常痛试验；Hargreaves热痛觉过敏试验、热板试验和甩尾试验；热异常痛冷板试验和丙酮滴试验）。以阿霉素（DOX）负载脂质纳米颗粒（LNPs/DOX）为代表的肿瘤纳米药物，以罗哌卡因（ROP）负载的LNPs （LNPs/ROP）为代表的疼痛纳米药物，验证了抑制皮下肿瘤生长可以缓解癌症疼痛，而延迟生长则不能，尽管与未治疗组相比有显著差异。此外，所有测试的行为结果都是一致的，其中von Frey测试被认为是最敏感的。提示疼痛相关行为测试可作为预测肿瘤纳米药物在体内治疗皮下肿瘤疗效的有力工具。

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引用次数: 0

A blood-brain barrier-penetrating nanoreactor for tumor microenvironment modulation, precise MR imaging and synergistic therapy of glioma 一种用于肿瘤微环境调节、精确磁共振成像和胶质瘤协同治疗的血脑屏障穿透纳米反应器

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-11-17 DOI: 10.1016/j.ijpx.2025.100448

Peipei Dou , Liang Chen , Yiyang Xie , Wenbei Xu , Xinran Zhang , Xiaomei Deng , Haiqing Xu , Jingran Li , Vincent Kawuribi , Shaohui Zheng , Kai Xu , Jing Zhang

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.

基于纳米材料的治疗策略已成为胶质瘤治疗的创新技术。然而，血脑屏障（BBB）的存在阻碍了药物对胶质瘤的有效递送，肿瘤微环境（TME）的缺氧状态显著降低了治疗效果。因此，在这项研究中，我们开发了一种新的活性氧（ROS）产生纳米平台响应TME。该平台利用介孔PtNi纳米颗粒（NPs）作为载体，装载螯合钆卟啉（Gd-HMME），在磁共振成像（MRI）指导下实现声动力和化学动力联合治疗。Tf-PtNi@Gd-HMME-PEG （TPGP）采用转铁蛋白（Tf）介导的转血脑屏障策略，精确靶向并穿透胶质瘤组织，促进肿瘤区域的t1加权增强成像。获得的MRI增强信号是对照组的1.64倍。同时，TPGP固有的声敏感性和酶样催化活性在超声刺激下产生大量ROS。这些ROS与TME中的过氧化氢相互作用产生有毒自由基，共同作用于肿瘤细胞，通过声动力和化学动力机制提供双重攻击，有效抑制肿瘤生长，改善肿瘤微环境。这项研究强调了TPGP作为靶向胶质瘤治疗的多功能纳米平台的潜力，将诊断成像与协同治疗相结合，以克服血脑屏障和缺氧TME。

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引用次数: 0

Preparation and in vitro property evaluation of NO-HA@ICG self-assembled nanoparticles for gas therapy synergized with phototherapy 光疗协同气体治疗用NO-HA@ICG自组装纳米粒子的制备及体外性能评价

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-11-15 DOI: 10.1016/j.ijpx.2025.100446

Jiamin Huang , Jianhu Jia , Qian Zhang , Xiaohui Tang , Qi Shen , Wenjun Su , Jing Zhao , Mei Wang

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.

气体疗法和光疗法的协同作用是癌症治疗领域的一种创新疗法，具有独特的治疗机制和应用特点。NO改善肿瘤血管，促进药物到达肿瘤部位，光疗产生的热量和ROS促进NO的释放，协同诱导癌细胞凋亡。本研究通过微流控设备制备了由NO供体和HA构建的自组装纳米颗粒，并将ICG包埋在纳米颗粒中，对其光疗效果和NO释放性能进行了评价。结果表明，NO-HA@ICG NPs +激光组比游离ICG和NO-HA@ICG NPs组产生更强的ROS和NO，具有协同效应。纳米颗粒NO有望改善肿瘤血管性，促进药物到达肿瘤部位，光疗释放的热量和ROS不仅能促进NO的释放，还能与NO协同诱导癌细胞凋亡。

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引用次数: 0

Oral delivery of chitosan/hyaluronic-acid-coated milk-derived exosomes for ulcerative-colitis amelioration 口服壳聚糖/透明质酸包被乳源性外泌体改善溃疡性结肠炎

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-11-13 DOI: 10.1016/j.ijpx.2025.100447

Chao Deng , Xinyi Cheng , Qingying Sun , Yeliaman Yeerbolati , Rui Zheng , Youyi Liu , Ying Yao , Yanbing Shen , Kewei Wang , Jianfeng Huang

Restoring intestinal-barrier homeostasis is crucial in treating ulcerative colitis (UC). Milk-derived exosomes, known for their potent biological properties, hold promise in promoting intestinal-barrier repair. However, their stability and targeting ability during gastrointestinal transit remain challenging. To address this, we engineered exosomes via layer-by-layer (LBL) encapsulation, enhancing their stability, controlled release, and targeted delivery. In a C57BL/6 J mouse model of UC induced by dextran sulfate sodium, oral administration of LBL-encapsulated milk-derived exosomes (LBL-Exos) significantly improved the intestinal barrier, including the physical, mucus, and immune barriers, thereby effectively alleviating the symptoms of UC, even at half the exosome dosage. These effects were also associated with reduced apoptosis and inhibition of the PI3K/AKT signaling pathway. This study demonstrates the therapeutic potential of engineered milk-derived exosomes in UC treatment, offering a promising approach for treating colitis and paving the way for the broader use of natural exosomes in related diseases.

恢复肠道屏障稳态是治疗溃疡性结肠炎（UC）的关键。乳源性外泌体以其强大的生物学特性而闻名，有望促进肠道屏障修复。然而，它们在胃肠道运输中的稳定性和靶向能力仍然具有挑战性。为了解决这个问题，我们通过层层（LBL）封装来设计外泌体，提高它们的稳定性，控制释放和靶向递送。在葡聚糖硫酸钠诱导UC的C57BL/6 J小鼠模型中，口服lbl包封乳源性外泌体（LBL-Exos）可显著改善肠道屏障，包括物理屏障、粘液屏障和免疫屏障，从而有效缓解UC的症状，即使是在一半的外泌体剂量下。这些作用还与减少细胞凋亡和抑制PI3K/AKT信号通路有关。本研究证明了工程乳源性外泌体在UC治疗中的治疗潜力，为治疗结肠炎提供了一种有希望的方法，并为在相关疾病中广泛使用天然外泌体铺平了道路。

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引用次数: 0

Biomimetic nanotherapy for P. gingivalis-infected oral squamous cell carcinoma: Photothermal therapy and immunoactivation via precise intracellular bacterial elimination 仿生纳米疗法治疗牙龈卟啉卟啉感染的口腔鳞状细胞癌：光热疗法和通过精确的细胞内细菌消除的免疫激活

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-11-12 DOI: 10.1016/j.ijpx.2025.100438

Zihan Dai , Qiaoxin Li , Longxuan Guo , Kaijing Zhong , Jing Cheng , Xiuhong Weng , Bo Cheng

Porphyromonas gingivalis (P. gingivalis) 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 P. gingivalis 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 P. gingivalis-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 P. gingivalis 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.

口腔鳞状细胞癌（OSCC）中的牙龈卟啉单胞菌（P. gingivalis）感染通过驱动化疗耐药、肿瘤进展和免疫抑制来破坏患者对标准治疗的反应。越来越多的研究证据——包括我们的临床OSCC活检染色——证实了瘤内牙龈假单胞菌定植和CXCL2过表达是预后不良的危险因素。因此，准确清除促瘤微生物，减轻免疫抑制是提高治疗效果的关键。受验证观察的启发，我们开发了一种独特的临床导向纳米颗粒平台（MC-MM@MPDA），该平台集成了精确的细胞内抗生素递送，光热肿瘤消融，光热杀菌和免疫激活。尽管人们对OSCC光热消融越来越感兴趣，但该平台是第一个利用光热治疗的双重抗肿瘤和抗菌功能，旨在实现针对牙龈假单胞菌感染的OSCC的靶向治疗。米诺环素（MC）被装载到介孔聚多巴胺（MPDA）纳米颗粒中，并被巨噬细胞膜包裹，使其能够选择性地归巢到感染的肿瘤部位，并被癌细胞有效吸收。随后，纳米平台利用光热效应消融肿瘤组织，消除细胞内细菌并诱导免疫原性细胞死亡（ICD）。ph触发的抗生素释放可根除残留细菌并释放细菌肿瘤相关抗原。与ICD产生的损伤相关分子模式（DAMPs）一起，这些信号重新编程了免疫抑制微环境，并建立了协同抗肿瘤网络。在牙龈假单胞菌感染的OSCC异种移植模型中，该平台显著抑制肿瘤生长，清除病原体负担，克服细菌介导的治疗耐药性。通过利用膜模拟靶向和协同光热免疫疗法，MC-MM@MPDA提供了一种可扩展、生物相容性和易于翻译的策略，以解决OSCC治疗中病原体驱动的障碍。

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引用次数: 0

Carrier-free multi-components self-delivery nanocomplex for tumor synergistic therapy 用于肿瘤协同治疗的无载体多组分自递送纳米复合物

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-11-12 DOI: 10.1016/j.ijpx.2025.100443

Pengkai Ma , Ziqi Jing , Xue Wang , Xiaoya Liu , Zirui Tan , Yujie Zhang , Zhijun Wang

Due to the intricate nature of tumors, developing multidrug delivery system to enhance synergistic therapy for tumors is urgently needed. Herein, we present a carrier-free nanocomplex (DHT NC@SF MPN), consisting of dihydrotanshinone-1 nanocrystals (DHT NC) combined with silybin-ferric metal-phenolic network coatings (SF MPN), for multidrug self-delivery and chemo/chemodynamic synergistic cancer therapy. The generated nanocomplex (DHT NC@SF MPN) was completely composed of three therapeutic ingredients: DHT (56.08 %), Sil (41.88 %), and Fe(III) (2.01 %) without incorporation of any nano-materials. It displayed spherical core-shell structure with particle size 262 nm and acid responding drug release. The nanocomplex could be efficiently uptaken by HGC-27 tumor cells through the lipid raft/caveolin mediated pathway. It exhibited stronger tumor cell proliferation inhibition, migration inhibition, cell apoptosis and ferroptosis compared with free drugs. On tumor bearing mice, it showed comparable anti-tumor efficacy with the commercial paclitaxel liposome while systemic toxicity was negligible. Therefore, the facile nanocarrier-free multidrug self-delivery nanoplatform shed light on developing advanced nanomedicine for tumor synergistic therapy.

由于肿瘤的复杂性，迫切需要开发多药给药系统来增强肿瘤的协同治疗。在此，我们提出了一种无载体纳米复合物（DHT NC@SF MPN），由二氢丹参酮-1纳米晶体（DHT NC）与水飞蓟宾-铁金属-酚网络涂层（SF MPN）组成，用于多药自我递送和化学/化学动力学协同癌症治疗。生成的纳米复合物（DHT NC@SF MPN）完全由三种治疗成分组成：DHT (56.08%), Sil（41.88%）和Fe(III)(2.01%)，而不掺入任何纳米材料。其呈球形核壳结构，粒径262 nm，具有酸响应释药特性。该纳米复合物可通过脂质筏/小窝蛋白介导途径被HGC-27肿瘤细胞有效吸收。与游离药物相比，具有较强的肿瘤细胞增殖抑制、迁移抑制、细胞凋亡和铁下垂作用。对荷瘤小鼠，其抗肿瘤效果与市售紫杉醇脂质体相当，而全身毒性可以忽略不计。因此，这种便捷的无纳米载体多药自释纳米平台为开发先进的纳米药物用于肿瘤协同治疗提供了新的思路。

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引用次数: 0

Boosting buccal drug absorption: Mechanistic insights into bilosome-mediated delivery 促进口腔药物吸收：生物体介导的给药机制

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-11-11 DOI: 10.1016/j.ijpx.2025.100444

Eleftheria Pantazoglou , Scarlett Zeiringer , Matteo Tollemeto , Nazanin Zanjanizadeh Ezazi , Zhongyang Zhang , Leticia Hosta-Rigau , Jette Jacobsen , Ramona Jeitler , Eva Roblegg , Line Hagner Nielsen

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. Ex vivo 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.

有效的口腔药物递送受到粘膜屏障特性的限制，需要创新的系统来增强通透性而不损害组织完整性。在这项研究中，由糖脱氧胆酸钠和磷脂酰胆碱组成的胆囊体被评估为口腔药物递送的纳米颗粒平台。用TR146口腔细胞系研究了它们的体外摄取。其物理化学性质稳定，无聚集现象。功能分析表明，它们能瞬间打开细胞-细胞连接，促进通过粘膜屏障的运输，同时将毒性降到最低。带有耗散监测的石英晶体微天平证实了与屏障成分的特定相互作用，这得到了观察到的桥粒连接和细胞摄取调节的支持。利用猪口腔粘膜进行的离体研究进一步显示出浓度依赖性分布。综上所述，这些结果表明，胆囊体是一个安全有效的促进口腔药物吸收的平台。

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引用次数: 0

Multifunctional saikosaponin D-liposomes for hepatocellular carcinoma: Formulation optimization, characterization, and in vitro/in vivo evaluation 用于肝细胞癌的多功能柴草皂苷d脂质体：配方优化、表征和体外/体内评价

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-11-11 DOI: 10.1016/j.ijpx.2025.100445

Kun Yu , Sicheng Huang , Guochun Yang , Junze Tang , Xiaoyu Zhao , Rui Pan , Hailiang Zhang , Menghan Xu , Xiaofei Li , Xin Cheng , Anguo Hou

The study aimed to construct saikosaponin D (SSD)-based liposomes modified with phosphatidic acid (PA) and poloxamer 407 (P407) (termed P407-SSD-Lps), and to evaluate their tumor-targeting ability and antitumor efficacy through in vitro and in vivo experiments. The preparation process and formulation of the P407-SSD-Lps were optimized using single-factor and orthogonal experimental designs, followed by systematic characterization. Their antitumor activity and targeting specificity were assessed through in vitro experiments. Additionally, the tumor-targeting capability, therapeutic efficacy, and biocompatibility of the P407-SSD-Lps were investigated in murine orthotopic hepatocellular carcinoma transplantation models. The P407-SSD-Lps optimized through single-factor and orthogonal experiments exhibited ideal physicochemical properties. In vitro results demonstrated that the P407-SSD-Lps enhanced cell membrane permeability and promoted cellular uptake in the HepG2 cells. Additionally, they significantly inhibited the HepG2 cells proliferation and induced apoptosis. In murine orthotopic hepatocellular carcinoma transplantation models, the P407-SSD-Lps exhibited prolonged tumor accumulation and demonstrated potent antitumor efficacy with favorable biocompatibility. When delivering doxorubicin (DOX), the system not only retained high biocompatibility but also exhibited enhanced therapeutic efficacy. Employing the SSD as both a liposomal membrane stabilizer and a therapeutic agent constituted a novel expansion of “drug-excipient integration” material applications. Moreover, the SSD-based P407-SSD-Lps system functioned as a stable and efficient multifunctional liposomal delivery system, offering innovative therapeutic avenues for hepatocellular carcinoma treatment.

本研究旨在构建以磷脂酸（PA）和波洛沙姆407 （P407）修饰的柴草皂苷D （SSD）为基础的脂质体（简称P407-SSD- lps），并通过体内外实验评价其肿瘤靶向能力和抗肿瘤效果。采用单因素和正交实验设计对P407-SSD-Lps的制备工艺和配方进行优化，并进行系统表征。通过体外实验评价其抗肿瘤活性和靶向特异性。此外，我们还在小鼠原位肝癌移植模型中研究了P407-SSD-Lps的肿瘤靶向能力、治疗效果和生物相容性。通过单因素和正交实验优化得到的P407-SSD-Lps具有理想的理化性能。体外实验结果表明，P407-SSD-Lps增强了HepG2细胞的细胞膜通透性，促进了细胞摄取。此外，它们还能显著抑制HepG2细胞的增殖，诱导细胞凋亡。在小鼠原位肝癌移植模型中，P407-SSD-Lps表现出较长时间的肿瘤积累，并表现出较强的抗肿瘤作用和良好的生物相容性。当输送阿霉素（DOX）时，该系统不仅保持了高生物相容性，而且表现出增强的治疗效果。将固态固态同时用作脂质体膜稳定剂和治疗剂，构成了“药物-赋形剂一体化”材料应用的新拓展。此外，基于ssd的P407-SSD-Lps系统作为一种稳定高效的多功能脂质体递送系统，为肝癌治疗提供了创新的治疗途径。

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