Journal of Drug Delivery Science and Technology最新文献_第3页

In silico–designed peptide targeting MDR1 (P-gp) restores chemosensitivity in colorectal cancer via chitosan nanoparticle delivery 硅片设计的靶向MDR1 （P-gp）肽通过壳聚糖纳米颗粒递送恢复结直肠癌的化疗敏感性

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-21 DOI: 10.1016/j.jddst.2026.108003

Hande Maden , Hilal Calik , Rabia Yilmaz Ozturk , Selcen Ari Yuka , Betül Zehra Temur , Özge Can , Gizem Dinler Doğanay , Rabia Cakir

Colorectal cancer is the second most common cause of cancer-related deaths worldwide. Most of these deaths are due to failure of chemotherapy caused by drug resistance and resulting tumor recurrence. Therefore, overcoming drug resistance is crucial for the successful treatment of colorectal cancer. In this study, the P5S3 peptide selected by bioinformatics analysis for inhibiting drug resistance and the 5-FU drug were loaded into chitosan nanoparticles and investigated in vitro on drug-resistant colorectal cancer cells. Firstly, P5S3 was identified as a peptide inhibitor by MDR1 binding site-specific molecular docking analyses and in silico prediction of biological and physicochemical properties. The peptide was synthesized using the solid phase synthesis method and characterized by RP-HPLC and LC-MS/MS. Chitosan nanoparticles loaded with 5-FU and P5S3 (5-FU/P5S3@CSNPs) were synthesized using an ionic gelation method and characterized using a ZetaSizer, FT-IR, FE-SEM, and UV–Vis. The 5-FU/P5S3@CSNPs were approximately 110 nm in size and spherical in shape, and had a good encapsulation efficiency and loading capacity. Furthermore, drug resistance was conferred to sensitive HCT-116 cells (HCT-116/FU) that were continuously exposed to 5-FU, and the development of drug resistance was confirmed by qPCR. The effect of 5-FU/P5S3@CSNPs on cell viability in HCT-116/FU cells and their inhibitory activities on MDR1 drug efflux pumps were analyzed by XTT and accumulation assay, respectively. Our results demonstrate that the 5-FU/P5S3@CSNPs had high anticancer potential against HCT-116/FU cells and high inhibition ability of MDR1. In conclusion, our findings suggest that 5-FU/P5S3@CSNPs offer a promising approach for the treatment of resistant colorectal cancer.

结直肠癌是全球癌症相关死亡的第二大常见原因。这些死亡大多是由于化疗失败引起耐药性和肿瘤复发。因此，克服耐药性对于大肠癌的成功治疗至关重要。本研究将生物信息学分析选择的抑制耐药的P5S3肽和5-FU药物负载到壳聚糖纳米颗粒中，并在体外对耐药的结直肠癌细胞进行了研究。首先，通过MDR1结合位点特异性分子对接分析和生物物理化学性质的计算机预测，P5S3被鉴定为肽抑制剂。采用固相法合成该肽，并采用反相高效液相色谱和LC-MS/MS对其进行了表征。采用离子凝胶法制备了负载5-FU和P5S3的壳聚糖纳米颗粒（5-FU/P5S3@CSNPs），并用ZetaSizer、FT-IR、FE-SEM和UV-Vis对其进行了表征。5-FU/P5S3@CSNPs的尺寸约为110 nm，呈球形，具有良好的封装效率和负载能力。此外，持续暴露于5-FU的敏感HCT-116细胞（HCT-116/FU）被赋予耐药性，并通过qPCR证实了耐药的发生。采用XTT法和积累法分别分析5-FU/P5S3@CSNPs对HCT-116/FU细胞活力的影响以及对MDR1药物外排泵的抑制作用。结果表明，5-FU/P5S3@CSNPs对HCT-116/FU细胞具有较高的抗癌潜力，对MDR1具有较高的抑制能力。总之，我们的研究结果表明，5-FU/P5S3@CSNPs为治疗耐药结直肠癌提供了一种有希望的方法。

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引用次数: 0

Preclinical development and evaluation of Uricase mRNA-loaded lipid nanoparticles for the treatment of hyperuricemia 载尿酸酶mrna脂质纳米颗粒治疗高尿酸血症的临床前开发和评估

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-20 DOI: 10.1016/j.jddst.2026.108029

Jing Zhang , Jing Wen , Tie Li , Junshuang Xu , Jinbiao Ma , Min Hong , Wei Li

Hyperuricemia (HU), a common metabolic disorder, is characterized by elevated serum uric acid (sUA) levels. Uricase, an enzyme that degrades uric acid(UA) into allantoin, is absent in humans due to a nonsense mutation. Messenger RNA (mRNA)-based protein replacement therapy, known for its efficiency and transient expression, has garnered significant research attention. This study focuses on developing a mRNA therapy for HU using human ancestral uricase ANC19, delivered via lipid nanoparticles (LNPs). We prepared ANC19-LNPs, characterized their physicochemical properties, and evaluated their expression and function in Huh7 cells. Results indicate successful preparation and characterization of ANC19-mRNA, which localizes to peroxisomes and demonstrates UA degradation capability in vitro. Biodistribution was validated in Balb/c mice. Concurrently, a HU mouse model was successfully established using siRNA-mediated knockdown of Uricase-mRNA. In HU mouse models, ANC19-LNPs achieved a 75.63 % UA degradation rate. To validate these promising findings in a more clinically relevant species, the therapy was evaluated in cynomolgus monkeys, where it also showed a therapeutic effect, the area under the curve (AUC) of the concentration-time curve for ANC19-LNPs was 32.647 h∗μg/mL compared to 67.074 h∗μg/mL for the negative control. Biochemical blood tests in cynomolgus monkeys confirmed the safety of ANC19-LNPs. In conclusion, we have successfully developed an effective mRNA-based protein replacement therapy for UA degradation, showing promising efficacy and safety in both in vitro and in vivo studies.

高尿酸血症（HU）是一种常见的代谢性疾病，其特征是血清尿酸（sUA）水平升高。尿酸酶是一种将尿酸（UA）降解为尿囊素的酶，由于无义突变而在人类中缺失。基于信使RNA （mRNA）的蛋白质替代疗法以其高效和瞬时表达而闻名，已经引起了人们的广泛关注。本研究的重点是利用人类祖先的尿酸酶ANC19，通过脂质纳米颗粒（LNPs）递送mRNA治疗HU。我们制备了ANC19-LNPs，表征了它们的理化性质，并评价了它们在Huh7细胞中的表达和功能。结果表明，成功制备并表征了ANC19-mRNA，该mrna定位于过氧化物酶体，并显示出体外UA降解能力。Balb/c小鼠体内生物分布验证。同时，通过sirna介导的敲低Uricase-mRNA，成功建立了HU小鼠模型。在HU小鼠模型中，ANC19-LNPs的UA降解率达到75.63%。为了在更多临床相关物种中验证这些有希望的发现，对食蟹猴进行了治疗评估，在那里它也显示出治疗效果，ANC19-LNPs的浓度-时间曲线下面积（AUC）为32.647 h∗μg/mL，而阴性对照为67.074 h∗μg/mL。食蟹猴血液生化检测证实了ANC19-LNPs的安全性。总之，我们已经成功开发了一种有效的基于mrna的蛋白替代疗法，用于UA降解，在体外和体内研究中都显示出良好的疗效和安全性。

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引用次数: 0

Optimization of β-sitosterol–based cationic liposomes for gene delivery in vitro and in vivo 体外和体内基因传递β-谷甾醇阳离子脂质体的优化

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-20 DOI: 10.1016/j.jddst.2026.108038

Jong-Soo Choi , Jae-Won Park , Dong Kyu Choi , Jin Hong Lee , Gi-Baek Kwon , Ji-Hoon Shin , Kyung-Oh Doh

Cationic cholesterol liposomes offer the advantage of binding affinity to nucleic acids and stability in the serum. Additionally, the cationic cholesterol serves as a helper lipid enhancing the bio distribution of lipid nanoparticles. β-sitosterol, with its branched C-24 ethyl group in the tail of the sterol backbone, influences membrane structure. Because of this structural difference, β-sitosterol containing LNPs may exhibit efficient cellular uptake and gene expression. Therefore, we synthesized the cationic sitosterol derivative through amidation of the 3-hydroxy group of β-sitosterol, followed by conversion to the nitrile, reduction of the nitrile and deprotection of the BOC group. The final compound was incorporated as a lipid component for the liposomal formulation. Replacing cationic cholesterol with the cationic sitosterol derivative in liposomes significantly enhanced gene delivery of plasmid DNA, mRNA and siRNA. The liposome comprising an equal ratio of cationic cholesterol and sitosterol (C1S1) exhibited 3–5 fold increases of GFP pDNA expression in CHO and HeLa cells compared to liposomes containing only cationic cholesterol or sitosterol. It also showed 1.5-fold increases of GFP mRNA expression in CHO and HeLa cells.

This improvement in gene delivery was attributed to 2-fold increase in cellular uptake and more efficient endosomal escape. However, in an in vivo model, the liposome formulated exclusively with cationic sitosterol demonstrated the highest mRNA expression. This discrepancy suggests that in vivo data cannot always be predicted through in vitro data likely due to physiological barriers such as reticuloendothelial system and serum aggregation in vivo.

阳离子胆固醇脂质体具有与核酸结合的亲和力和在血清中的稳定性。此外，阳离子胆固醇作为辅助脂质增强脂质纳米颗粒的生物分布。β-谷甾醇，其支链的C-24乙基在甾醇主链尾部，影响膜结构。由于这种结构差异，含有β-谷甾醇的LNPs可能表现出有效的细胞摄取和基因表达。因此，我们通过对β-谷甾醇的3-羟基进行酰胺化，然后转化为腈，还原腈，去保护BOC基团，合成了阳离子谷甾醇衍生物。最终化合物作为脂质成分纳入脂质体制剂。在脂质体中，用阳离子谷甾醇衍生物代替阳离子胆固醇可显著增强质粒DNA、mRNA和siRNA的基因传递。与只含有阳离子胆固醇或谷固醇的脂质体相比，含有相同比例阳离子胆固醇和谷固醇（C1S1）的脂质体在CHO和HeLa细胞中的GFP pDNA表达增加了3-5倍。CHO和HeLa细胞中GFP mRNA表达增加1.5倍。这种基因传递的改善归因于细胞摄取增加2倍和更有效的内体逃逸。然而，在体内模型中，仅用阳离子谷甾醇配制的脂质体显示出最高的mRNA表达。这种差异表明体内数据并不总是通过体外数据来预测，这可能是由于网状内皮系统和体内血清聚集等生理障碍。

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引用次数: 0

Ion-paired asiatic acid hydrogel facilitates high-quality wound healing through diverse synergistic effects 离子配对的亚细亚酸水凝胶通过多种协同作用促进高质量的伤口愈合

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-19 DOI: 10.1016/j.jddst.2026.108034

Mingming Li , Suhong Fu , Jiaxin Chen , Xinxing Sun , Yang Chen , Lei Yang

High-quality wound healing is a primary clinical goal, yet it remains difficult to achieve reliably with current treatments. For this purpose, this study developed an ion-paired asiatic acid (AA) hydrogel specially for wound healing and systematically evaluated its pharmacodynamic efficacy both in vitro and in vivo. The formulation strategy involved screening organic amines as counter-ions using an ex vivo stratum corneum-removed skin model. Triethanolamine was identified as the optimal counterion, maximizing AA penetration into local tissue while minimizing systemic permeation via the formation of an ion-pair as confirmed by Nuclear Magnetic Resonance. The resulting hydrogel exhibited ideal properties for wound application, as characterized by its water vapor transmission rate, swelling ratio, degradability ratio, and water retention. In vitro, the hydrogel accelerated wound closure by stimulating cellular proliferation and migration, promoting vascular differentiation, and exhibiting selective antibacterial efficacy against S. aureus. In a rat full-thickness skin defect model, the hydrogel effectively facilitated scarless healing, which was mechanistically linked to collagen remodeling (indicated by a higher proportion of type III relative to type I collagen), suppression of TNF-α-mediated inflammation, and downregulation of TGF-β-driven fibrosis. Collectively, this work establishes a strategically designed ion-pair hydrogel system that coordinates key healing processes, offering a promising strategy for achieving reliable, high-quality wound regeneration.

高质量的伤口愈合是一个主要的临床目标，但目前的治疗方法仍然难以可靠地实现。为此，本研究研制了一种专门用于伤口愈合的离子配对亚洲果酸（AA）水凝胶，并对其体内体外药效学效果进行了系统评价。配方策略涉及筛选有机胺作为反离子使用离体角质层去除皮肤模型。三乙醇胺被确定为最佳反离子，通过核磁共振证实，通过形成离子对，最大限度地提高AA对局部组织的渗透，同时最大限度地减少全身渗透。所制备的水凝胶具有良好的透气性、溶胀率、可降解率和保水性。在体外，水凝胶通过刺激细胞增殖和迁移，促进血管分化，加速伤口愈合，并对金黄色葡萄球菌表现出选择性抗菌作用。在大鼠全层皮肤缺损模型中，水凝胶有效促进无疤痕愈合，其机制与胶原重塑（III型胶原相对于I型胶原比例更高）、抑制TNF-α-介导的炎症和下调TGF-β驱动的纤维化有关。总的来说，这项工作建立了一个战略性设计的离子对水凝胶系统，协调关键的愈合过程，为实现可靠、高质量的伤口再生提供了一个有希望的策略。

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引用次数: 0

Sustained-release sodium alginate-based metformin/bentonite nanocomposite hydrogel for enhanced wound healing 缓释海藻酸钠基二甲双胍/膨润土纳米复合水凝胶促进伤口愈合

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-19 DOI: 10.1016/j.jddst.2026.108035

Zahra Rezanejad Gatabi , Mehri Mirhoseini , Mozhgan Abasi , Mohammad Shokati Sayyad , Pedram Ebrahimnejad

Hydrogels are promising wound dressings, yet traditional hydrogels often lack optimal mechanical strength and antimicrobial activity. We developed a novel sodium alginate-based metformin-loaded bentonite (Met-Ben) nanocomposite hydrogel to enhance wound healing. Metformin was encapsulated within bentonite nanoparticles via ion-exchange, achieving an entrapment efficiency of 75.6 % and a drug-loading value of 27.7 %. The nanoparticles had an average size of 364.5 nm and a zeta potential of −8.6 mV. The hydrogel exhibited an increased swelling ratio over 4 h and showed approximately 65 % degradation over 14 days. Sustained metformin release followed Korsmeyer-Peppas kinetics (n = 0.3541, indicating Fickian diffusion). ATR-FTIR and DSC confirmed the chemical integrity and amorphous state of encapsulated metformin. In vitro cytotoxicity assays confirmed its biocompatibility. In vivo, the Met-Ben hydrogel significantly accelerated wound closure (85 % at day 14), increased collagen deposition (p < 0.05, histological scoring), and enhanced fibroblast maturation, re-epithelialization, and neovascularization compared with the control. Gene expression analysis showed downregulation of TNF-α and IL-1β and upregulation of TGF-β (p < 0.01), supporting modulation of inflammation and promotion of tissue regeneration. This study introduces the first sodium alginate–bentonite–metformin nanocomposite hydrogel, offering a dual-action bioactive and structural platform for full-thickness wound healing.

水凝胶是一种很有前途的伤口敷料，但传统的水凝胶往往缺乏最佳的机械强度和抗菌活性。我们开发了一种新型的海藻酸钠基二甲双胍负载膨润土（Met-Ben）纳米复合水凝胶，以促进伤口愈合。通过离子交换将二甲双胍包埋在膨润土纳米颗粒中，包埋效率为75.6%，载药量为27.7%。纳米粒子的平均尺寸为364.5 nm， zeta电位为−8.6 mV。水凝胶在4小时内溶胀率增加，在14天内降解率约为65%。二甲双胍持续释放符合Korsmeyer-Peppas动力学（n = 0.3541，表明菲克扩散）。ATR-FTIR和DSC证实了包封二甲双胍的化学完整性和无定形状态。体外细胞毒性试验证实了其生物相容性。在体内，与对照组相比，Met-Ben水凝胶显著加速伤口愈合（第14天85%），增加胶原沉积（p < 0.05，组织学评分），促进成纤维细胞成熟、再上皮化和新生血管形成。基因表达分析显示TNF-α和IL-1β下调，TGF-β上调（p < 0.01），支持炎症调节和促进组织再生。本研究首次介绍了海藻酸钠-膨润土-二甲双胍纳米复合水凝胶，为全层伤口愈合提供了双重作用的生物活性和结构平台。

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引用次数: 0

Development of antibiotic dry powder inhalers formulations for the treatment of respiratory bacterial infections: A comprehensive review 用于治疗呼吸道细菌感染的抗生素干粉吸入器配方的发展：综合综述

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-19 DOI: 10.1016/j.jddst.2026.108041

Mingjun Li , Min Zhao , Yaochen Deng , Zengming Wang , Hui Zhang , Conghui Li , Yi Cheng , Nan Liu , Shirui Mao , Aiping Zheng

Lower respiratory tract infections (LRTIs) constitute the fourth leading cause of mortality worldwide, resulting in over two million deaths annually. Bacterial pathogens are implicated in approximately 30 % of these fatalities. Dry powder inhalers (DPIs) facilitate the attainment of elevated pulmonary concentrations of antibiotics through targeted particle deposition at the site of infection, thereby optimizing local drug exposure while concurrently reducing systemic drug levels. Effective pulmonary drug delivery necessitates powders possessing optimal aerodynamic characteristics. Achieving such properties in dry powder inhalation particles is possible through diverse formulation strategies and advanced inhaler technologies. This targeted approach to drug delivery facilitates high-dose localized treatment while concurrently minimizing the potential for systemic adverse effects and the development of antibiotic resistance. This review outlines the global landscape of antibiotic DPIs, detailing marketed products and those in development. It highlights how particle-engineering and functional excipients address API constraints to enhance lung deposition. Future innovations are likely to focus on new delivery methods and strategic combinations, such as antibiotics combined with mucolytics or bacteriophages, to improve the treatment of drug-resistant respiratory infections.

下呼吸道感染是全世界第四大死亡原因，每年造成200多万人死亡。这些死亡中约30%与细菌性病原体有关。干粉吸入器（dpi）通过在感染部位的靶向颗粒沉积促进提高肺部抗生素浓度，从而优化局部药物暴露，同时降低全身药物水平。有效的肺给药需要粉末具有最佳的空气动力学特性。通过不同的配方策略和先进的吸入器技术，可以实现干粉吸入颗粒的这种特性。这种靶向给药方法促进了高剂量的局部治疗，同时最大限度地减少了潜在的全身不良反应和抗生素耐药性的发展。本综述概述了抗生素dpi的全球概况，详细介绍了已上市产品和正在开发的产品。它强调了粒子工程和功能赋形剂如何解决API限制以增强肺沉积。未来的创新可能集中在新的给药方法和战略组合上，例如抗生素与解粘剂或噬菌体联合使用，以改善耐药呼吸道感染的治疗。

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引用次数: 0

Co-delivery of gefitinib and curcumin via zein-based nanoparticles to enhance EGFR signaling inhibition and prevent cancer progression 吉非替尼和姜黄素通过基于玉米蛋白的纳米颗粒共同递送增强EGFR信号抑制和预防癌症进展

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-19 DOI: 10.1016/j.jddst.2026.108040

Pei-Ling Liu , Jia-Lin Wang , Yi-Ying Dong , Hong Liu , Jin-Ju Lei , Bin Xu , Xin-Ru Liao , Di Han , Zi-Hao He , Si-Xue Cheng

Epidermal growth factor receptor (EGFR) targeted cancer therapy offers high selectivity and reduced toxicity. However, the therapeutic efficacy is compromised by the poor bioavailability of hydrophobic drugs such as gefitinib (GEF), and the acquired resistance. Curcumin (CUR) can sensitize tumor cells toward EGFR inhibitors and reverse drug resistance, but its application is also hindered by low solubility. To address these limitations, we developed a zein-based drug delivery system for the co-delivery of GEF and CUR. The dual-drug loaded zein-based nanoparticles (GEF/CUR@ZNP) decorated by pectin were prepared by self-assembly. GEF/CUR@ZNP exhibited a mean diameter less than 300 nm, featuring a narrow size distribution and an encapsulation efficiency higher than 80 %. The therapeutic efficacy was evaluated in vitro using PC-9 cells. Compared with free drugs, GEF/CUR@ZNP led to significantly enhanced cellular uptake, resulting in improved induction of cancer cell apoptosis and higher efficiency in downregulation of proteins promote cancer progression (e.g., Sp1, Bcl-2, VEGF, Snail, and CD44). To evaluate the efficacy of the drug delivery system in a context more relevant to clinical settings, we evaluated the EGFR inhibition efficacy by using the blood samples containing circulating tumor cells (CTCs) from non-small cell lung cancer (NSCLC) patients, and immunofluorescence labeling confirmed that GEF/CUR@ZNP achieved most effective suppression of EGFR expression. These findings demonstrate that zein-based co-delivery of GEF and CUR can overcome multiple barriers to targeted cancer therapy, and offer a clinically relevant strategy for enhancing antitumor efficacy and personalizing cancer treatment.

表皮生长因子受体（EGFR）靶向癌症治疗具有高选择性和低毒性。然而，吉非替尼（GEF）等疏水药物的生物利用度较差，以及获得性耐药影响了治疗效果。姜黄素（Curcumin， CUR）可使肿瘤细胞对EGFR抑制剂增敏并逆转耐药性，但其溶解度低也阻碍了其应用。为了解决这些问题，我们开发了一种基于玉米蛋白的药物递送系统，用于GEF和CUR的共同递送。通过自组装制备了由果胶修饰的双药载玉米蛋白纳米颗粒（GEF/CUR@ZNP）。GEF/CUR@ZNP平均直径小于300 nm，尺寸分布窄，封装效率高于80%。体外应用PC-9细胞评价其治疗效果。与游离药物相比，GEF/CUR@ZNP显著增强了细胞摄取，从而改善了对癌细胞凋亡的诱导，并提高了对促进癌症进展的蛋白（如Sp1、Bcl-2、VEGF、Snail、CD44）的下调效率。为了在与临床环境更相关的背景下评估药物递送系统的功效，我们通过使用来自非小细胞肺癌（NSCLC）患者的含有循环肿瘤细胞（CTCs）的血液样本来评估EGFR抑制功效，免疫荧光标记证实GEF/CUR@ZNP对EGFR表达的抑制效果最有效。这些研究结果表明，基于玉米蛋白的GEF和CUR联合给药可以克服靶向癌症治疗的多重障碍，为提高抗肿瘤疗效和个性化癌症治疗提供了临床相关的策略。

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引用次数: 0

Choline-retinoic acid ionic liquid as a potential therapy agent for acute promyelocytic leukemia 胆碱维甲酸离子液体作为治疗急性早幼粒细胞白血病的潜在药物

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-19 DOI: 10.1016/j.jddst.2026.108039

Hongyu Zhu , Liuyang Wang , Jingyang Zhao , Zhiguo Su , Kiichi Sato , Xiaoyi Wang , Songping Zhang

All-trans retinoic acid (Ra)-mediated differentiation therapy remains the first-line treatment for acute promyelocytic leukemia (APL). However, Ra must be administered orally due to its extremely poor aqueous solubility. The absorption of Ra is influenced by various factors, which can result in variable bioavailability and, consequently, variable therapeutic effects. Accordingly, the development of a parenteral Ra formulation is highly demanded. In the current study, Choline-retinoic acid ([Cho][Ra]), which significantly improved the water solubility of Ra, was systemically evaluated as the pro-differentiation and pro-apoptosis agent for APL cells. In vitro cellular studies demonstrate that compared to Ra, [Cho][Ra] induced a more pronounced G0-G1 phase cell cycle arrest, leading to a greater inhibition of cell proliferation. Concurrently, it also promoted a higher percentage of cells to undergo differentiation. Furthermore, [Cho][Ra] showed superior efficacy in inducing late-stage apoptosis, which was associated with a more severe loss of mitochondrial membrane potential. [Cho][Ra] treatment also induced higher reactive oxygen species (ROS) levels, which suggests that ROS generation may be a key mechanistic contributor to both cell apoptosis and differentiation. These findings suggest that [Cho][Ra] could be a promising alternative to Ra, overcoming the solubility limitations and improving its efficacy in treating leukemia.

全反式维甲酸（Ra）介导的分化治疗仍然是急性早幼粒细胞白血病（APL）的一线治疗方法。然而，由于Ra的水溶性极差，必须口服给药。Ra的吸收受到多种因素的影响，这可能导致不同的生物利用度，从而导致不同的治疗效果。因此，迫切需要研制一种注射用Ra制剂。本研究系统评价了胆碱维甲酸（Choline-retinoic acid, [Cho][Ra]）对APL细胞的促分化和促凋亡作用，胆碱维甲酸能显著提高Ra的水溶性。体外细胞研究表明，与Ra相比，[Cho][Ra]诱导更明显的G0-G1期细胞周期阻滞，从而更大程度地抑制细胞增殖。同时，它也促进了更高比例的细胞进行分化。此外，[Cho][Ra]在诱导晚期细胞凋亡方面表现出优越的疗效，而晚期细胞凋亡与更严重的线粒体膜电位丧失有关。[Cho][Ra]处理还诱导了更高的活性氧（ROS）水平，这表明ROS的产生可能是细胞凋亡和分化的关键机制因素。这些发现表明[Cho][Ra]可能是一种有希望的Ra替代品，克服溶解度限制并提高其治疗白血病的疗效。

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引用次数: 0

Carbon dots in nasal delivery: Emerging strategies for enhanced therapeutic efficacy 碳点鼻腔给药：提高治疗效果的新策略

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-17 DOI: 10.1016/j.jddst.2026.108028

Nejva Kaid , Gamze Camlik , Yildiz Ozsoy

Intranasal drug delivery has emerged as an effective, non-invasive strategy for targeting both systemic circulation and the central nervous system (CNS), offering a means to bypass first-pass metabolism and the blood–brain barrier (BBB). This route can significantly improve drug bioavailability and therapeutic outcomes. Among the various nanomaterials investigated for intranasal applications, carbon dots (CDs) have attracted growing interest due to their ultra-small size, tunable surface functionalization, strong photoluminescence, high aqueous solubility, chemical stability, favorable biocompatibility, and minimal cytotoxicity. These features make CDs particularly well suited for both therapeutic delivery and theranostic applications. This review provides a comprehensive overview of recent advances in CD-based intranasal delivery systems, with emphasis on their ability to enhance transport across biological barriers, improve drug stability and targeting, and support real-time imaging. Key strategies in formulation design, surface functionalization, and preclinical performance are discussed, alongside critical limitations affecting clinical translation, including incomplete mechanistic understanding, safety evaluation gaps, and challenges related to reproducibility. Together, these insights provide a framework to guide the rational design of CD-enabled intranasal systems and to inform future efforts aimed at translating preclinical advances into clinically applicable nasal drug delivery technologies.

鼻内给药已成为针对体循环和中枢神经系统（CNS）的一种有效的非侵入性策略，提供了一种绕过首过代谢和血脑屏障（BBB）的方法。该途径可显著提高药物的生物利用度和治疗效果。在研究鼻内应用的各种纳米材料中，碳点（cd）由于其超小尺寸、可调节的表面功能化、强光致发光、高水溶性、化学稳定性、良好的生物相容性和最小的细胞毒性而引起了越来越多的兴趣。这些特点使得cd特别适合于治疗传递和治疗应用。本文综述了基于cd的鼻内给药系统的最新进展，重点介绍了它们增强跨越生物屏障的转运、提高药物稳定性和靶向性以及支持实时成像的能力。讨论了配方设计、表面功能化和临床前性能方面的关键策略，以及影响临床翻译的关键限制，包括不完整的机制理解、安全性评估差距和与可重复性相关的挑战。总之，这些见解为指导CD-enabled鼻内系统的合理设计提供了一个框架，并为未来将临床前进展转化为临床应用的鼻内给药技术提供了信息。

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引用次数: 0

Emerging therapies for lung adenocarcinoma: Mechanistic and efficacy insights from spheroid-based in vitro models 肺腺癌的新疗法：基于球体的体外模型的机制和疗效见解

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-17 DOI: 10.1016/j.jddst.2026.108030

Pooja Sawant , Ratnesh Jain , Prajakta Dandekar

The persistent challenges of drug resistance, tumor heterogeneity, and poor predictability of traditional 2D and animal models underscore the urgent need for innovative strategies in development of safe and efficacious anti-cancer interventions. In recent years, novel drug delivery systems (NDDS) such as nanoparticles, liposomes, antibody-drug conjugates, as well as inhalable formulations have emerged as promising approaches to enhance drug targeting, efficacy, and safety, particularly in hard-to-treat malignancies like lung cancer. Concurrently, 3D in vitro tumor spheroid models have gained recognition for their ability to recapitulate key features of the tumor microenvironment, including cell-cell and cell-matrix interactions, oxygen gradients, and drug penetration barriers. This manuscript presents a comprehensive compilation of the NDDS that have been evaluated using spheroid models and demonstrated substantial therapeutic potential, with many demonstrating translational success in subsequent animal studies. By highlighting the correlation between spheroid-based screening outcomes and in vivo efficacy, we aim to highlight the importance of spheroid models as efficient, reproducible, and ethically favorable tools for early-phase drug evaluation. Overall, this review emphasizes the dual relevance of NDDS and in vitro spheroid systems in advancing precision oncology while promoting the reduction of animal usage in research.

传统2D和动物模型的耐药、肿瘤异质性和较差的可预测性的持续挑战强调了开发安全有效的抗癌干预措施的创新策略的迫切需要。近年来，新型药物传递系统（NDDS）如纳米颗粒、脂质体、抗体-药物偶联物以及可吸入制剂已成为增强药物靶向性、有效性和安全性的有希望的方法，特别是在肺癌等难以治疗的恶性肿瘤中。同时，体外三维肿瘤球体模型因其概括肿瘤微环境关键特征的能力而获得认可，包括细胞-细胞和细胞-基质相互作用、氧梯度和药物穿透屏障。本文介绍了一篇全面的NDDS汇编，这些NDDS已经用球体模型进行了评估，并显示出巨大的治疗潜力，其中许多在随后的动物研究中证明了转化成功。通过强调基于球体的筛选结果与体内疗效之间的相关性，我们的目标是强调球体模型作为早期药物评估的高效、可重复性和伦理上有利的工具的重要性。总之，这篇综述强调了NDDS和体外球体系统在推进精准肿瘤学和促进减少动物实验使用方面的双重相关性。

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