Journal of Drug Delivery Science and Technology最新文献_第10页

Disulfiram-loaded nanoemulsions for enhanced anticancer efficacy in peritoneal carcinomatosis: Design, optimization, in vitro and in vivo evaluation 负载双硫仑的纳米乳剂增强腹膜癌的抗癌效果：设计、优化、体外和体内评价

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-06 DOI: 10.1016/j.jddst.2026.107994

Ping Wang , Yue Wang , Changjiang Li , Zhongcheng Ke , Yan Gong , Boyuan Liu , Meng Wang , Xiangqun Jin

Disulfiram (DSF), an FDA-approved anti-alcoholism drug, has demonstrated potent anticancer activity against peritoneal carcinomatosis. However, its therapeutic potential is severely hampered by poor aqueous solubility and instability. Nanoemulsion system provides a promising platform to overcome these challenges. Herein, this study developed and optimized a DSF-loaded nanoemulsions (DSF-NE) to enhance the therapeutic efficacy of DSF in peritoneal carcinomatosis. The optimized DSF-NE exhibited several formulation advantages, including a small particle size (∼84 nm), narrow size distribution (∼0.1), high encapsulation efficiency (>90 %) and sustained-release behavior. Subsequently, cytotoxicity assays against MGC-803, SKOV-3 and Caco-2 cells revealed that DSF-NE significantly enhanced cytotoxic effects compared to DSF, with IC₅₀ values reduced by 74 %, 62 % and 56 %, respectively. Consistently, DSF-NE achieved a tumor inhibition rate 108.57 % higher than that of DSF in a murine peritoneal carcinomatosis model. The main mechanism involves enhanced cellular uptake of DSF-NE, which promotes ROS generation and subsequently triggers apoptosis. Collectively, these findings highlight DSF-NE as a nanoformulation strategy that not only improves the therapeutic performance of DSF in peritoneal carcinomatosis but also offers broader implications in the development of effective delivery systems for poorly soluble and unstable drugs.

双硫仑（DSF）是一种fda批准的抗酒精中毒药物，已经显示出对腹膜癌的有效抗癌活性。然而，其水溶性差和不稳定性严重阻碍了其治疗潜力。纳米乳液系统为克服这些挑战提供了一个有希望的平台。本研究开发并优化了DSF负载纳米乳（DSF- ne），以提高DSF对腹膜癌的治疗效果。优化后的DSF-NE具有多种配方优势，包括粒径小（~ 84 nm）、粒径分布窄（~ 0.1 nm）、包封效率高（> 90%）和缓释性能。随后，对MGC-803、SKOV-3和Caco-2细胞的细胞毒实验显示，DSF- ne与DSF相比显著增强了细胞毒作用，IC50值分别降低了74%、62%和56%。在小鼠腹膜癌模型中，DSF- ne的抑瘤率比DSF高108.57%。主要机制涉及增强细胞对DSF-NE的摄取，从而促进ROS的产生并随后触发细胞凋亡。总的来说，这些发现强调了DSF- ne作为一种纳米制剂策略，不仅可以提高DSF在腹膜癌中的治疗效果，而且还可以为开发难溶性和不稳定药物的有效递送系统提供更广泛的意义。

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引用次数: 0

Evaluation of a novel liposome nano-formulation of quercetin with optimized cholesterol level [Lipo-Que] for intravenous administration and in vivo toxicity in mice 新型槲皮素脂质体纳米配方优化胆固醇水平[lipoo - que]静脉给药及小鼠体内毒性评价

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-06 DOI: 10.1016/j.jddst.2026.107984

V. Jenitha , D. David Wilson , G. Monith , Nampalli Babu Kokelavani , Ramachandran , S. Viswanathan , M. Srividhya , Vijay Nandana , V. M. Berlin Grace

Quercetin, a synthetic flavonoid phytochemical, has gained attention for its anti-cancer properties due to its anti-oxidant and anti-inflammatory effects, as well as its molecular actions on cancer signaling pathways. However, the therapeutic efficacy of orally administered quercetin is limited due to metabolic conversions. This study aimed to develop a novel liposomal formulation for quercetin administration via intravenous injection, utilizing thermosensitive phospholipids, cholesterol, polyethylene glycol, and folic acid. Two formulations were created (Lipo-Que 7:2:1 and Lipo-Que 5:4:1) and compared against free quercetin [Free-Que] for in vitro characterization, bioactivity, and biocompatibility. Both formulations were tested for anti-oxidant potency and cytotoxicity on a human lung cancer cell line and normal fetal lung fibroblast cells. The optimized dose of 25 μM quercetin was further analyzed for anti-cancer effects. Results showed that Lipo-Que 7:2:1 had significantly higher antioxidant potency and cytotoxicity (IC50 of 5.10 ± 0.19 μM) compared to Lipo-Que 5:4:1 and Free-Que. The formulations demonstrated high drug entrapment efficiency and confirmed successful encapsulation through HPLC, UV–Vis, and FTIR analyses. Additionally, Lipo-Que 7:2:1 showed enhanced quercetin release at higher temperatures and acidic pH, mimicking the cancer microenvironment. In vivo toxicity studies indicated that Lipo-Que 7:2:1 was safer than Free-Que, with no significant toxic effects observed.

Applications

These findings suggest that optimized liposomal quercetin formulations enhance therapeutic efficacy while maintaining stability under hyperthermic conditions (up to 45 °C). The biocompatibility results support their potential clinical application as intravenous drug candidates for lung cancer treatment.

槲皮素是一种合成的类黄酮植物化学物质，由于其抗氧化和抗炎作用以及在癌症信号通路中的分子作用而受到关注。然而，口服槲皮素的治疗效果是有限的，由于代谢转化。本研究旨在利用热敏磷脂、胆固醇、聚乙二醇和叶酸，开发一种新的槲皮素静脉注射给药脂质体。制备了两种制剂（lipoo - que 7:2:1和lipoo - que 5:4:1），并与游离槲皮素[free - que]进行体外表征、生物活性和生物相容性的比较。在人肺癌细胞系和正常胎儿肺成纤维细胞上测试了两种配方的抗氧化能力和细胞毒性。进一步分析最佳剂量25 μM槲皮素的抗癌作用。结果表明，与lipoo - que 5:4:1和Free-Que相比，lipoo - que 7:2:1具有显著的抗氧化能力和细胞毒性（IC50为5.10±0.19 μM）。通过HPLC、UV-Vis和FTIR分析，证实该制剂具有较高的药物包封效率。此外，Lipo-Que 7:2:1显示在高温和酸性pH下槲皮素释放增强，模拟癌症微环境。体内毒性研究表明lipoo - que 7:2:1比Free-Que更安全，没有观察到明显的毒性作用。这些发现表明，优化的槲皮素脂质体制剂可提高治疗效果，同时在高温条件下（高达45°C）保持稳定性。生物相容性结果支持其作为肺癌静脉注射候选药物的潜在临床应用。

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引用次数: 0

Lactoferrin-functionalized bioinspired grapefruit-extracellular vesicles for targeted delivery of pterostilbene in lung cancer therapy 乳铁蛋白功能化的生物启发西柚细胞外囊泡靶向递送紫檀芪在肺癌治疗中

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-05 DOI: 10.1016/j.jddst.2026.107991

Eman M. Nour , Salma E. El-Habashy , Ahmed M.R. Fath El-Bab , Basant A. Bakr , Riham M. El-Moslemany , Amal H. El-Kamel

Lung cancer remains the primary cause of cancer-related mortality worldwide, emphasizing the pressing need for novel phytoconstituent-based therapeutic strategies. This study investigates the lung anti-cancer potential of pterostilbene (PS), a bioactive phytochemical, incorporated into a bioinspired delivery system to improve its efficacy. PS was encapsulated within grapefruit-derived extracellular vesicles (GEV) for the development of novel (PS-GEV). Two isolation techniques were investigated: polymer precipitation and a microfluidic-assisted approach, with polymer precipitation offering superior scalability and efficiency. The resulting PS-GEV, isolated using PEG-precipitation, exhibited excellent colloidal stability, a high encapsulation efficiency exceeding 95 %, and a nanoscale particle size (30.85 ± 8.15 nm). To enhance tumor targeting and therapeutic outcomes, lactoferrin functionalization was performed (LF/PS-GEV). These modified nanocarriers showed a zeta potential of −4.03 ± 0.22 mV, particle size of 48.49 ± 13.14 nm, and a sustained release profile with 59.3 ± 4.93 % PS release over 24 h. In vitro studies on A549 lung cancer cells demonstrated enhanced cellular uptake, reduced cell viability, and inhibited cancer cell migration. The developed vesicles demonstrated high hemocompatibility. In vivo evaluation in a urethane-induced lung cancer mouse model confirmed improved therapeutic outcomes, with LF/PS-GEV treatment significantly reducing the tumor weight-to-body weight ratio (5.05 ± 0.37) compared to the untreated group. Additionally, pro-angiogenic (VEGF) and proliferative markers (cyclin D1) were downregulated, while apoptotic markers BAX (1.89 ± 0.04-fold) and caspase-3 (4.91 ± 0.09-fold) were upregulated. Histological and immunohistochemical analyses confirmed notable suppression of chemotherapy resistance-related p53 protein. Collectively, these findings highlight LF/PS-GEV as a potent, active targeting nanotherapeutic platform for effective lung cancer management through enhanced therapeutic efficacy and tumor-specific action.

肺癌仍然是世界范围内癌症相关死亡的主要原因，强调迫切需要新的基于植物成分的治疗策略。本研究探讨了紫檀芪（pterostilbene， PS）作为一种具有生物活性的植物化学物质，加入到生物激励给药系统中，以提高其抗肺癌的潜力。PS被包裹在葡萄柚源性细胞外囊泡（GEV）中，用于开发新的（PS-GEV）。研究了两种分离技术：聚合物沉淀法和微流体辅助方法，其中聚合物沉淀法具有优越的可扩展性和效率。通过聚乙二醇沉淀法分离得到的PS-GEV具有优异的胶体稳定性，包封效率超过95%，粒径为纳米级（30.85±8.15 nm）。为了提高肿瘤靶向性和治疗效果，进行了乳铁蛋白功能化（LF/PS-GEV）。这些修饰的纳米载体的zeta电位为- 4.03±0.22 mV，粒径为48.49±13.14 nm， 24小时的缓释率为59.3±4.93%。在体外对A549肺癌细胞的研究表明，细胞摄取增强，细胞活力降低，癌细胞迁移受到抑制。发育的囊泡表现出高度的血液相容性。在氨基甲酸乙酯诱导的肺癌小鼠模型中进行的体内评估证实了治疗效果的改善，与未治疗组相比，LF/PS-GEV治疗显著降低了肿瘤重量与体重比（5.05±0.37）。促血管生成（VEGF）和增殖标志物（cyclin D1）下调，凋亡标志物BAX（1.89±0.04倍）和caspase-3（4.91±0.09倍）上调。组织学和免疫组织化学分析证实化疗耐药相关p53蛋白明显抑制。总之，这些发现突出了LF/PS-GEV作为一种有效的、活性靶向的纳米治疗平台，通过增强治疗效果和肿瘤特异性作用，有效地管理肺癌。

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引用次数: 0

Effect of ionizable lipid head and tail group modification on mRNA delivery efficiency 可电离脂质头尾基团修饰对mRNA传递效率的影响

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-05 DOI: 10.1016/j.jddst.2026.107981

Soan Park , Kanghun Lee , Hyun-Jung An , Enhui Lin , Sugyeom Kim , Hyeongseok Kim , Siheon Jeong , Snehagni Roy , Yeon Woo Kang , Jaehyuk Yang , Seung-Woo Lee , Gi-Ra Yi , Hyomin Lee , Dong-won Seo , Dong Soo Hwang , Joongoo Lee , Jeong Wook Lee

Ionizable lipids are crucial components of lipid nanoparticles (LNPs) that significantly impact mRNA therapeutic delivery efficiency. While SM-102 and ALC-0315 demonstrated success in Moderna and Pfizer/BioNTech COVID-19 vaccines, the relationship between their structural features and delivery performance remains unclear. We systematically modified SM-102 by incorporating ALC-0315 features: converting its asymmetric tail to a symmetric structure and replacing the 2-aminoethanol head group with ALC-0315's 4-aminobutanol group. Both modifications decreased mRNA delivery efficiency in vitro and in vivo compared to unmodified SM-102. To investigate the underlying mechanisms, we conducted independent labeling assays using DiI to track LNP internalization, and Cy3 to monitor mRNA cargo delivery. Our results revealed that while tail-modified LNPs exhibited rapid and sustained cellular uptake (DiI signal), head-modified LNPs showed relatively lower internalization. Interestingly, despite the lower uptake, the head-modified LNPs achieved significantly higher GFP expression. These findings demonstrate a clear discrepancy between internalization quantity and translation efficiency. We conclude that the absolute amount of internalized mRNA is not the sole determinant of delivery success; rather, the effective translation (functional delivery) is more critical. This study suggests that LNP structural optimization should prioritize post-internalization functional release and translation quality over simple uptake efficiency.

可电离脂质是脂质纳米颗粒（LNPs）的重要组成部分，它显著影响mRNA的治疗递送效率。虽然SM-102和ALC-0315在Moderna和辉瑞/BioNTech的COVID-19疫苗中取得了成功，但它们的结构特征与递送性能之间的关系尚不清楚。我们将ALC-0315的不对称尾部转化为对称结构，并用ALC-0315的4-氨基丁醇基团取代2-氨基乙醇基团，对SM-102进行了系统的修饰。与未修饰的SM-102相比，这两种修饰都降低了mRNA在体外和体内的传递效率。为了研究潜在的机制，我们进行了独立的标记分析，使用DiI来跟踪LNP的内化，使用Cy3来监测mRNA的货物递送。我们的研究结果显示，虽然尾部修饰的LNPs表现出快速和持续的细胞摄取（DiI信号），但头部修饰的LNPs表现出相对较低的内化。有趣的是，尽管摄取较低，头部修饰的LNPs获得了显著更高的GFP表达。这些研究结果表明，内化量与翻译效率之间存在明显的差异。我们得出结论，内化mRNA的绝对数量不是递送成功的唯一决定因素；相反，有效的翻译（功能交付）更为关键。本研究表明，LNP结构优化应优先考虑内化后的功能释放和翻译质量，而不是简单的吸收效率。

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引用次数: 0

Fabrication of hairpin DNA-functionalized polydopamine-coated gold nanoparticles as a theranostic nanoplatform for effective delivery of daunorubicin: Binding affinity, drug release and cytotoxicity study 发夹dna功能化聚多巴胺包覆金纳米颗粒作为柔红霉素有效递送治疗纳米平台的制备：结合亲和力、药物释放和细胞毒性研究

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-05 DOI: 10.1016/j.jddst.2026.107982

Jie Liu , Xiangtai Wang , Yushu Wu , Lixia Yuan , Xiusheng Zhang , Xiaoyan Wu , Min Liu

Enhanced drug efflux in breast cancer cells is mediated by multiple transporters (e.g., P-glycoprotein), and the breast cancer resistance protein (BCRP) represents a key biomarker and therapeutic target among them. To address this, we constructed a pH-responsive multifunctional nanocarrier, hpDNA-PDA-AuNPs, by functionalizing polydopamine-coated gold nanoparticles with hairpin DNA (hpDNA) to deliver daunorubicin (DAU). This system integrated diagnostic imaging with three therapeutic modalities: chemotherapy, gene therapy, and photothermal therapy. It demonstrated specific targeting toward BCRP mRNA, achieving a detection limit of 0.64 nM. Spectroscopic and calorimetric analyses revealed that DAU binds more strongly to hpDNA-PDA-AuNPs than to PDA-AuNPs, which was attenuated under acidic conditions. The hpDNA-PDA-AuNPs + DAU system exhibited pH-responsive drug release, enhanced by NIR irradiation and BCRP mRNA. The combined treatment demonstrated potent synergistic antitumor activity with nuclear accumulation of DAU, offering a promising platform to overcome multidrug resistance via programmable drug release, gene silencing, and photothermal ablation.

乳腺癌细胞内药物外排增强是由多种转运蛋白（如p -糖蛋白）介导的，其中乳腺癌耐药蛋白（breast cancer resistance protein， BCRP）是关键的生物标志物和治疗靶点。为了解决这个问题，我们构建了一个ph响应的多功能纳米载体，hpDNA- pda - aunps，通过发夹DNA （hpDNA）功能化聚多巴胺包被的金纳米颗粒来传递柔红霉素（DAU）。该系统将诊断成像与三种治疗方式相结合：化疗、基因治疗和光热治疗。对BCRP mRNA具有特异性靶向作用，检测限为0.64 nM。光谱分析和量热分析表明，DAU与hpDNA-PDA-AuNPs的结合比与PDA-AuNPs的结合更强，在酸性条件下减弱。hpDNA-PDA-AuNPs + DAU系统表现出ph响应性药物释放，近红外照射和BCRP mRNA增强了药物释放。联合治疗显示出强大的协同抗肿瘤活性和核累积的DAU，提供了一个有前途的平台，通过可编程的药物释放，基因沉默和光热消融克服多药耐药。

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引用次数: 0

Dual release of miRNA-424-3p and doxorubicin using layer-by-layer stimuli-responsive dendritic mesoporous nanoparticles 利用一层一层的刺激响应树突状介孔纳米颗粒双重释放miRNA-424-3p和阿霉素

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-05 DOI: 10.1016/j.jddst.2026.107986

Oznur Akbal Vural , Tayfun Vural , Vicente Martí-Centelles , Estela Climent , Alba García-Fernández , Ramón Martínez-Máñez

The prevalence of cancer is on the rise on a global scale, and lung cancer represents one of the most common types of cancer worldwide that leads to high cancer-related deaths. Over the past decade, nanotechnology has made tremendous progress in cancer treatment. Moreover, combination therapy, including chemotherapy and gene therapy, has turned out to be a promising strategy that could enhance therapeutic efficacy in the treatment of lung adenocarcinoma. The tumor-suppressive miRNA-424-3p has demonstrated to significantly downregulate galectin-3 (Gal3) which is an anti-apoptotic protein and highly expressed in A549 cells. This has been shown to promote apoptosis, decrease proliferation, and increase sensitivity to the chemotherapeutic drug doxorubicin (Dox). However, miRNA-424-3p-based combination therapies with Dox have not yet been reported. Since dendritic mesoporous silica nanoparticles (DMSNs) have the potential to act as carriers for nucleic acids and drugs simultaneously, in this study we have successfully introduced for the first time anti-Gal3 functionalized DMSNs for the co-delivery of miRNA-424-3p and Dox protected with a layer-by-layer polyethyleneimine and poly-L-lysine coating. Whereas there is no or minimal Dox and miRNA release under neutral pH from the nanoparticles, conversely, a significant delivery of Dox and miRNA is seen in lysosomal extract medium. The effects of the co-delivery system, i.e. miRNA-424-3p and Dox, on A549 cells is evaluated by analyzing cell proliferation, cellular uptake, cell apoptosis assay, and the expression of related proteins and genes. The results demonstrate that miRNA-424-3p effectively transfected into A549 lung cancer cells, dramatically reducing the expression of Gal3 at the protein level. Forward transfection of the cell line with the DMSN loaded with miRNA-424-3p and Dox causes both a decrease in cell viability and an increase in apoptosis induction. Our data shows that the designed DMSN has a good performance as a combined drug and gene delivery system for cancer therapy.

癌症的患病率在全球范围内呈上升趋势，肺癌是全球最常见的癌症类型之一，导致与癌症相关的高死亡率。在过去的十年里，纳米技术在癌症治疗方面取得了巨大的进步。此外，包括化疗和基因治疗在内的联合治疗已被证明是一种有前途的策略，可以提高治疗肺腺癌的疗效。肿瘤抑制miRNA-424-3p已被证明可显著下调半乳糖凝集素-3 (Gal3)， Gal3是一种在A549细胞中高表达的抗凋亡蛋白。这已被证明可以促进细胞凋亡，减少增殖，并增加对化疗药物阿霉素（Dox）的敏感性。然而，基于mirna -424-3p与Dox的联合治疗尚未报道。由于树突状介孔二氧化硅纳米颗粒（DMSNs）具有同时作为核酸和药物载体的潜力，在本研究中，我们首次成功地引入了抗gal3功能化的DMSNs，用于共同递送miRNA-424-3p和Dox，并使用一层一层的聚乙烯亚胺和聚l -赖氨酸涂层保护。在中性pH下，纳米颗粒没有或只有很少的Dox和miRNA释放，相反，在溶酶体提取物培养基中可以看到Dox和miRNA的大量释放。通过分析细胞增殖、细胞摄取、细胞凋亡实验以及相关蛋白和基因的表达，评估miRNA-424-3p和Dox共递送系统对A549细胞的影响。结果表明，miRNA-424-3p有效转染A549肺癌细胞，在蛋白水平上显著降低Gal3的表达。负载miRNA-424-3p和Dox的dmn正向转染细胞系可导致细胞活力下降和细胞凋亡诱导增加。我们的数据表明，所设计的DMSN作为一种药物和基因联合传递系统在癌症治疗中具有良好的性能。

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引用次数: 0

Microalgae-derived vesicles as potential carriers for therapeutic biomacromolecules 微藻衍生囊泡作为治疗性生物大分子的潜在载体

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-05 DOI: 10.1016/j.jddst.2026.107985

Mária Klacsová , Krisztina Sebők-Nagy , Tibor Páli , Marcela Chovancová , László Almásy , Daniela Uhríková

Microalgae-derived vesicles (AGVs) were investigated as potential carriers for therapeutic biomacromolecules. AGVs were prepared by rehydration of a lyophilisate of proteolipid ghost membranes from Dunaliella tertiolecta and subsequent extrusion or sonication. Based on our results, extrusion is suggested to be a more suitable method because of the low loss of the lipid and protein content. Applying small-angle neutron scattering and dynamic and electrophoretic light scattering, we found that the formed AGVs are spherical, unilamellar, with moderate polydispersity, and a negative surface charge of −27 mV. EPR findings show that they retain the membrane dynamics, and possibly the degree of lipid chain saturation, of the ‘mother’ algal cells. The drug-binding efficiency of the reconstructed AGVs was tested for two model biomacromolecules, DNA and BSA, using an ethidium bromide exclusion assay and tryptophane autofluorescence, respectively. The electrostatic interaction between AGVs and DNA polyanion was mediated by Ca²⁺ ions, while for the interaction of BSA with AGVs hydrophobic interactions are assumed to play a dominant role. For both macromolecules tested, 40 % binding of the total drug amount was achieved by passive incubation, which indicates that reconstructed AGVs might expand the repertoire of potential delivery systems for therapeutic biomacromolecules.

研究了微藻衍生囊泡（agv）作为治疗性生物大分子的潜在载体。agv是由杜氏藻蛋白脂鬼膜冻干液再水化，然后挤压或超声制备的。根据我们的研究结果，挤出法是一种更合适的方法，因为它的脂肪和蛋白质含量损失较小。采用小角中子散射、动态光散射和电泳光散射等方法研究发现，制备的agv呈球形、单层、多分散性适中，表面负电荷为- 27 mV。EPR结果表明，它们保留了“母”藻细胞的膜动力学，可能还有脂链饱和的程度。采用溴化乙啶排除法和色氨酸自身荧光法分别检测重组agv对DNA和BSA两种模型生物大分子的药物结合效率。agv与DNA多阴离子之间的静电相互作用是由Ca2+离子介导的，而BSA与agv的相互作用被认为是疏水相互作用起主导作用。对于这两种被测试的大分子，通过被动孵育可以达到总药物量的40%，这表明重建的agv可能会扩大治疗性生物大分子的潜在递送系统。

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引用次数: 0

pH-responsive magnetic cyclodextrin-liposome nanoplatforms for stabilization and targeted delivery of topotecan ph响应磁环糊精脂质体纳米平台稳定和靶向递送拓扑替康

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-03 DOI: 10.1016/j.jddst.2026.107976

Bilsen Tural , Erdal Ertaş , Ali Kuruçay , Burhan Ateş , Servet Tural

Topotecan (TPT), a potent anticancer agent, suffers from rapid hydrolysis of its active lactone ring under physiological conditions, severely limiting its clinical efficacy. To address this challenge, we developed a novel pH-responsive, magnetic drug delivery system integrating β-cyclodextrin-functionalized Fe₃O₄ nanoparticles (Fe₃O₄@β-CD) and liposomes. Fe₃O₄@β-CD nanoparticles were synthesized via chemical co-precipitation and then loaded with TPT via host-guest complexation. The resulting Fe₃O₄@β-CD@TPT complexes were encapsulated into liposomes using the sonication method to increase drug stability, maintain the stable lactone form, and achieve controlled release. Characterization by Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Fourier Transform Infrared Spectroscopy (FTIR), High-Performance Liquid Chromatography (HPLC), and Vibrating Sample Magnetometry (VSM) confirmed the successful formulation. In vitro drug release studies demonstrated a diffusion-controlled release profile, while the pH responsiveness of the system was primarily governed by pH-dependent drug stabilization and loading efficiency rather than pronounced differences in release kinetics. Cytotoxicity assays against MCF-7 breast cancer cells showed that the Fe₃O₄@β-CD@TPT@Liposome formulation exhibited significantly lower IC₅₀ values compared to free TPT and Fe₃O₄@β-CD@TPT complexes. These results highlight the potential of the magnetic cyclodextrin-liposome hybrid platform as an effective strategy for the targeted and controlled delivery of pH-sensitive chemotherapeutics such as topotecan.

拓扑替康（Topotecan， TPT）是一种有效的抗癌药物，其活性内酯环在生理条件下会迅速水解，严重限制了其临床疗效。为了解决这一挑战，我们开发了一种新型的ph响应磁给药系统，将β-环糊精功能化的Fe3O4纳米颗粒（Fe3O4@β- cd）和脂质体整合在一起。采用化学共沉淀法合成Fe3O4@β-CD纳米颗粒，并通过主客体络合负载TPT。利用超声法将所得Fe3O4@β-CD@TPT配合物包封到脂质体中，提高药物稳定性，保持内酯形态稳定，实现控释。通过透射电镜（TEM）、动态光散射（DLS）、傅里叶变换红外光谱（FTIR）、高效液相色谱（HPLC）和振动样品磁强计（VSM）等表征方法证实了该配方的成功。体外药物释放研究显示了扩散控制的释放特征，而系统的pH响应性主要由pH依赖的药物稳定性和负载效率决定，而不是释放动力学的显着差异。对MCF-7乳腺癌细胞的细胞毒性试验表明，与游离TPT和Fe3O4@β-CD@TPT复合物相比，Fe3O4@β-CD@TPT@脂质体制剂的IC50值显着降低。这些结果突出了磁性环糊精-脂质体混合平台作为ph敏感化疗药物（如拓扑替康）靶向和控制递送的有效策略的潜力。

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引用次数: 0

Zein nanoparticles with bioadhesive potential for oral administration of propranolol: in vitro, in vivo and ex vivo investigations 具有生物粘附潜力的玉米蛋白纳米颗粒用于口服心得安：体外、体内和离体研究

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-02 DOI: 10.1016/j.jddst.2026.107978

Thaís Cruz Ramalho, Igor Frederico da Silveira Ramos, Talissa Brenda de Castro Lopes, Marcília Pinheiro da Costa, Hercília Maria Lins Rolim

Oral administration is a common route for medications but faces challenges such as pH variations and enzymatic activity in the gastrointestinal tract. Zein nanoparticles, a biocompatible plant-based protein, emerge as a promising solution to overcome these barriers and enhance the bioavailability of drugs such as propranolol, a beta-blocker with low solubility and bioavailability. This study evaluated the safety of zein nanoparticles for the oral delivery of propranolol through hemocompatibility, cytotoxicity, and ecotoxicity tests, as well as their mucoadhesive efficacy in porcine small intestine. The hemocompatibility test showed that both propranolol-loaded nanoparticles (NZ-PROP) and drug-free nanoparticles (NZ-EMP) did not cause damage to red blood cells, with results comparable to the negative control (0.9 % saline). In cytotoxicity assays using the Caco-2 cell line (human colorectal epithelial adenocarcinoma), both the nanoparticles and free propranolol demonstrated 100 % cell viability across all tested concentrations (15.625–250 μg mL⁻¹). In ecotoxicity tests using Artemia salina, free propranolol caused 100 % mortality of nauplii at concentrations of 62.5, 250, and 500 μg mL⁻¹, whereas the nanoparticles showed viability at all tested concentrations, indicating reduced toxicity. The mucoadhesive strength of the nanoparticles in porcine small intestine was higher than that of free propranolol, with a maximum detachment force of 0.2585 ± 0.05 N cm⁻² and an adhesion work of 0.0381 ± 0.002 mN × m, supporting prolonged drug release. These findings suggest that zein nanoparticles are safe and effective for the oral delivery of drugs with low permeability.

口服给药是一种常见的药物途径，但面临着诸如胃肠道pH变化和酶活性等挑战。玉米蛋白纳米颗粒是一种具有生物相容性的植物蛋白，有望克服这些障碍，提高药物的生物利用度，如低溶解度和生物利用度的β受体阻滞剂心得安。本研究通过血液相容性、细胞毒性和生态毒性测试来评估玉米蛋白纳米颗粒口服给药心得安的安全性，以及它们在猪小肠中的黏附效果。血液相容性试验表明，负载普萘洛尔的纳米颗粒（NZ-PROP）和不含药物的纳米颗粒（NZ-EMP）都不会对红细胞造成损伤，结果与阴性对照（0.9%生理盐水）相当。在使用ccao -2细胞系（人类结直肠上皮腺癌）进行的细胞毒性试验中，纳米颗粒和游离心得安在所有测试浓度（15.625-250 μg mL−1）下均显示出100%的细胞活力。在使用盐蒿的生态毒性试验中，游离的普萘洛尔在62.5、250和500 μg mL−1浓度下导致nauplii 100%死亡，而纳米颗粒在所有测试浓度下都显示出活力，表明毒性降低。纳米颗粒在猪小肠中的黏附强度高于游离的心得安，最大离体力为0.2585±0.05 N cm−2，黏附功为0.0381±0.002 mN × m，有利于延长药物释放时间。这些研究结果表明，玉米蛋白纳米颗粒对于低通透性药物的口服递送是安全有效的。

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引用次数: 0

Drug delivery system based on phase change material: thermo-responsive controlled release and multimodal synergistic therapy 基于相变材料的给药系统：热响应控释和多模式协同治疗

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-02 DOI: 10.1016/j.jddst.2025.107967

Xuelai Zhang, Zongpeng Li, Jun Ji

Conventional cancer therapies suffer from severely constrained clinical efficacy due to severe off-target toxicity, prevalent multidrug resistance, and inherent limitations of monotherapy. Phase change materials (PCMs) provide novel paradigms to overcome these constraints through thermo-responsive controlled drug release and synergistic multimodal therapeutic mechanisms. PCMs exhibit inherent biocompatibility, biodegradability, high drug-loading capacity, tunable melting points, and cost-effectiveness, effectively preventing premature payload leakage while enabling controllable thermo-responsive release, thereby enhancing therapeutic efficacy. This review comprehensively addresses the construction methodologies and design principles of PCM-based nanoplatforms, which function as stringent gatekeepers and efficient payload delivery systems. It details innovative applications in combinatorial anticancer therapies including photothermal-chemotherapy, photodynamic therapy (PDT), and chemodynamic therapy (CDT). Furthermore, surface functionalization and microenvironment modulation strategies enhance tumor-selective accumulation and deep-tissue penetration efficiency. By systematically integrating the precision release attributes of PCMs with multimodal synergistic strategies, this work establishes new paradigms for overcoming tumor resistance and reducing systemic toxicity. Its extensible design framework and performance-boosting mechanisms hold significant promise for advancing clinical translation of next-generation intelligent drug delivery systems.

传统的癌症治疗由于严重的脱靶毒性、普遍的多药耐药以及单一治疗的固有局限性，其临床疗效受到严重限制。相变材料（PCMs）通过热响应性控制药物释放和协同多模态治疗机制为克服这些限制提供了新的范例。PCMs具有固有的生物相容性、可生物降解性、高载药量、可调熔点和成本效益，可有效防止载药量过早泄漏，同时实现可控的热响应释放，从而提高治疗效果。本文综述了基于pcm的纳米平台的构建方法和设计原则，该平台作为严格的看门人和有效的有效载荷传递系统。它详细介绍了在组合抗癌治疗中的创新应用，包括光热化疗、光动力治疗（PDT）和化学动力治疗（CDT）。此外，表面功能化和微环境调节策略可提高肿瘤选择性积累和深层组织渗透效率。通过系统地将PCMs的精准释放特性与多模态协同策略相结合，本工作为克服肿瘤耐药和降低全身毒性建立了新的范例。其可扩展的设计框架和性能提升机制为推进下一代智能给药系统的临床转化带来了巨大的希望。

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引用次数: 0