Journal of Drug Delivery Science and Technology最新文献_第2页

Amphiphile-drug interplay: Enhanced solubility and drug-tailored self-assembly for delivery applications 两亲体-药物相互作用：增强溶解度和药物定制自组装递送应用

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-23 DOI: 10.1016/j.jddst.2026.108036

Angela Cerulo, Nicola Antonio Di Spirito, Nino Grizzuti, Rossana Pasquino

During the last three decades, the design of refined nanosized drug delivery systems employed peculiar temperature-responsive synthetic copolymers, Pluronics, capable to mimic biological systems. Biocompatibility and biodegradability, along with the possibility of opportunely tailoring the desired features of these macromolecules, can be exploited to develop carriers able to improve the solubility and the bioavailability of hydrophobic drugs. As passive agents, Pluronics have a high drug loading capacity in water and low immunogenicity, but they can also play a more active role by reacting to temperature changes. Within specific ranges of concentration, Pluronic aqueous solutions can be injected in liquid form and become soft solids at body temperature, allowing to modulate the drug release. The presence of additives can modify the thermal response of Pluronic molecules in water, possibly sensitizing the system to other stimuli (e.g., pH). In this work, the addition of hydrophobic Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) – ibuprofen (IBU), ibuprofen sodium salt (IBUNa), diclofenac potassium (DK) – in a 45 wt% Pluronic F68 aqueous solution was investigated by rheology, Differential Scanning Calorimetry (DSC), surface tension and wettability measurements. Pluronic F68 significantly increased the solubility of the drug in water. The thermo-reversible, self-assembling process was followed and phase transitions were identified through rheological oscillatory and steady measurements and calorimetric evaluations at different drug concentrations and temperatures. The effect of pH was also discussed by varying the drug type and its concentration. Lastly, empirical phase diagrams for the drug/Pluronic aqueous solutions were built.

在过去的三十年中，精细纳米级药物传递系统的设计采用了特殊的温度响应合成共聚物Pluronics，能够模拟生物系统。生物相容性和生物可降解性，以及适当地定制这些大分子所需特征的可能性，可以用来开发能够提高疏水药物的溶解度和生物利用度的载体。Pluronics作为被动制剂，在水中具有较高的载药能力和较低的免疫原性，但它们也可以通过对温度变化的反应发挥更积极的作用。在特定的浓度范围内，Pluronic水溶液可以以液体形式注射，并在体温下变成软固体，从而调节药物释放。添加剂的存在可以改变Pluronic分子在水中的热响应，可能使系统对其他刺激（例如pH值）敏感。在这项工作中，通过流变学、差示扫描量热法（DSC）、表面张力和润湿性测量，研究了疏水非甾体抗炎药（NSAIDs）——布洛芬（IBU）、布洛芬钠盐（IBUNa）、双氯芬酸钾（DK）在45 wt% Pluronic F68水溶液中的添加。Pluronic F68显著提高了药物在水中的溶解度。随后进行了热可逆自组装过程，并通过流变振荡和稳态测量以及不同药物浓度和温度下的量热评估确定了相变。还讨论了pH值对药物种类和浓度的影响。最后，建立了药物/Pluronic水溶液的经验相图。

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引用次数: 0

Insights into conditions affecting the skin viscoelasticity for the design of polymeric microneedles with optimal mechanical properties 深入了解影响皮肤粘弹性的条件，以设计具有最佳机械性能的聚合物微针

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2026-01-22 DOI: 10.1016/j.jddst.2026.108050

Júlia Elizabeth Pigatto Stringhi, Bianca Costa Bernardo Port, Thiago Caon

Although polymeric microneedles (MNs) have gained attention for vaccination and deposition of large molecules into the skin, insufficient mechanical properties have limited the number of devices reaching the market. Fracture of needles resulting in premature drug release and inability to pierce the skin have been the most common problems. Given that MNs represent an emerging technology, the lack of standardized formulation characterization protocols coupled with the current gaps in the regulatory framework can lead to the market introduction of MNs with questionable quality. The selection of inappropriate membrane models for MN penetration assays, skin regions differing from the intended application site, problems in tissue processing and inadequate storage conditions may be the cause of mechanical failures, which were discussed in detail in this study. Some disease states can also make the skin more rigid or more elastic, demanding adjustments in MN design (composition, dimensions). In the first situation, the mechanical properties of MNs should be improved and then approaches such as polymer combinations instead of a single polymer; the addition of sugars, nano/microparticles and polymer cross-linking reactions could be considered. When a skin is more elastic, adjustments in MN dimensions (needle length/tip) are recommended. Different from other studies that have analyzed approaches for improving the mechanical properties of MNs, this study brings further data on conditions able to affect the skin viscoelasticity/structure, which would impact MN performance. Therefore, more rational devices could be designed, reducing the rate of refusal of products in the commercialization phase as well as clinical complications.

尽管聚合物微针（MNs）在疫苗接种和大分子沉积到皮肤上得到了关注，但机械性能不足限制了进入市场的设备数量。针头断裂导致药物过早释放和无法刺穿皮肤是最常见的问题。鉴于纳米粒子是一种新兴技术，缺乏标准化的配方表征协议，加上目前监管框架中的空白，可能导致市场上引入质量可疑的纳米粒子。在锰渗透试验中选择不合适的膜模型、皮肤区域与预期应用部位不同、组织处理中的问题以及不适当的储存条件可能是机械故障的原因，这些都在本研究中进行了详细讨论。某些疾病状态也会使皮肤变得更坚硬或更有弹性，这就需要调整MN的设计（成分、尺寸）。在第一种情况下，应提高纳米颗粒的力学性能，然后采用聚合物组合代替单一聚合物的方法；可以考虑添加糖、纳米/微粒和聚合物交联反应。当皮肤更有弹性时，建议调整MN尺寸（针长/针尖）。与其他研究分析改善MN力学性能的方法不同，本研究提供了影响MN性能的皮肤粘弹性/结构的条件的进一步数据。因此，可以设计出更合理的器械，减少商业化阶段产品的拒绝率，减少临床并发症。

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引用次数: 0

Engineering and translational evaluation of A Novel Albumin-binding variable domain of heavy chain-only antibody for half-life extension 一种新型白蛋白结合可变结构域延长重链抗体半衰期的工程及翻译评价

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.2026.108044

Chengkai Yin , Tianyan Liu, Dan Yu, Yuanyuan Yan, Xuelei Pi, Panpan Sun, Hongna Chen, Jiarui Yang, Zhenzhong Wang, Zhihang Liu

Therapeutic proteins often exhibit rapid clearance from circulation, necessitating frequent dosing and impairing patient adherence. Here, we aimed to develop an albumin-binding VHH (variable domain of heavy chain-only antibody) to extend protein half-life via FcRn(neonatal Fc receptor)-mediated recycling, using follicle-stimulating hormone (FSH) as a model. Anti-HSA VHHs were isolated from a naïve alpaca phage library (with cross-reactivity to cynomolgus serum albumin, Cyno-SA) and characterized via surface plasmon resonance (SPR) for binding affinity. AlphaFold3-predicted VHH-HSA complex structures were validated by alanine-scanning mutagenesis. Pharmacokinetics (PK) were assessed in hFcRn-transgenic mice and cynomolgus monkeys, and translational utility was tested using the lead VHH-scFSH fusion (FSH-m7). The lead VHH bound human/Cyno-SA with high affinity, extending systemic exposure and reducing clearance in monkeys. FSH-m7 retained bioactivity, showed prolonged half-life (vs. wild-type FSH) with lower Cmax in humanized mice, and induced dose-dependent ovarian growth and higher estradiol in juvenile rats at equivalent molar doses. This HSA-binding VHH enables robust cross-species half-life extension of protein therapeutics while preserving activity, providing a generalizable platform for engineering albumin-binding biologics to support less frequent dosing and improved adherence.

治疗性蛋白通常表现出快速清除循环，需要频繁给药和损害患者的依从性。本研究以促卵泡激素（FSH）为模型，旨在开发一种结合白蛋白的VHH（仅重链可变结构域抗体），通过FcRn（新生儿Fc受体）介导的再循环延长蛋白质半衰期。从naïve羊驼噬菌体文库（与食狼血清白蛋白Cyno-SA具有交叉反应性）中分离出抗hsa vhs，并通过表面等离子体共振（SPR）对其结合亲和力进行了表征。通过丙氨酸扫描诱变验证了alphafold3预测的VHH-HSA复合物结构。在hfcrn转基因小鼠和食蟹猴中评估了药代动力学（PK），并使用VHH-scFSH融合体（FSH-m7）检测了转化效用。铅VHH以高亲和力结合人/Cyno-SA，延长全身暴露并减少猴子清除。在人源化小鼠中，FSH-m7保留了生物活性，表现出较长的半衰期（与野生型FSH相比）和较低的Cmax，并在相同摩尔剂量的幼年大鼠中诱导剂量依赖性卵巢生长和较高的雌二醇。这种结合hsa的VHH能够在保持活性的同时，延长蛋白质治疗药物的跨物种半衰期，为工程白蛋白结合生物制剂提供一个可推广的平台，以支持更少的给药频率和更好的依从性。

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引用次数: 0

Solubility enhancement of curcumin using PLA-grafted Hibiscus rosa-sinensis mucilage as a biocompatible amphiphilic copolymer 用pla接枝的芙蓉浆液作为生物相容性两亲共聚物增强姜黄素的溶解度

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.2026.108033

Biswasarathi Basak, Laxmi Kumari, Trishna Bal, Shreya Sharma, Akash Mondal, Joydeep Bhattacharyya

Green synthesized biocompatible polymers of amphiphilic nature can be used for enhancing the solubility and permeability of BCS Class-IV drugs. Thus, different grades of novel polylactic acid (PLA) grafted Hibiscus rosasinensis leaf mucilage (HLM) amphiphilic graft copolymer (HLM-g-PLA) were synthesized for improving the solubility and permeability characteristics of drugs like Curcumin. Optimized grade G1 was characterized using FTIR, ¹³C NMR, TGA, XRD, OCA and DLS. The critical micelle concentration (CMC) of G1 was found to be low indicating surfactant properties which were evidenced by its ability to stabilize colloidal dispersion. In vitro drug release study revealed 62.86 % of curcumin (CUR) release for more than 20 h, indicating sustained release properties, following Korsmeyer-Peppas model, indicating nonfickian diffusion with n > 0.5. The solubility and permeability of CUR were enhanced to 6.2013 ± 1.8142 μg/ml from 0.5254 ± 0.0342 μg/ml and 15.754 ± 0.7877 % respectively, in the presence of G1. The optimized grade G1 exhibited antimicrobial activity against Staphylococcus aureus and Escherichia coli with anti-inflammatory and hemocompatible properties. G1 also exhibited wound healing with no traces of scars and full hair growth within 11 days, indicating its biocompatible nature, thereby indicating the application of such natural polysaccharide modified amphiphilic graft copolymers as an effective pharmaceutical excipient.

绿色合成的两亲性生物相容性聚合物可用于提高BCS iv类药物的溶解度和渗透性。为此，合成了不同等级的新型聚乳酸（PLA）接枝芙蓉叶胶（HLM）两亲接枝共聚物（HLM-g-PLA），以改善姜黄素等药物的溶解度和通透性。采用FTIR、13C NMR、TGA、XRD、OCA、DLS等对优化后的G1级产品进行了表征。G1的临界胶束浓度（CMC）较低，表明其具有稳定胶体分散的能力。体外释药研究显示，62.86%的姜黄素（CUR）释放时间超过20 h，具有缓释特性，符合korsmemeyer - peppas模型，具有n >； 0.5的非黏性扩散。在G1的作用下，CUR的溶解度和通透性分别由0.5254±0.0342 μg/ml和15.754±0.7877%增强至6.2013±1.8142 μg/ml。优化后的G1级菌株对金黄色葡萄球菌和大肠杆菌具有抗菌活性，具有抗炎和血液相容性。G1在11天内伤口愈合，无疤痕痕迹，毛发完全生长，表明其具有生物相容性，从而表明这种天然多糖修饰的两亲性接枝共聚物作为一种有效的药用赋形剂的应用。

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引用次数: 0

Development and evaluation of Strychni semen total alkaloid-loaded transfersomes for targeted articular delivery in osteoarthritis 马钱子总生物碱转运体用于骨关节炎靶向关节传递的研制与评价

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.2026.108046

Jiazhen Zhu , Haonan Zhang , Jinmin Lin , Yuqi Wang , Zheng Shi , Fanzhu Li , Wendong Yao

Strychni semen contains bioactive total alkaloids effective against osteoarthritis (OA). However, their utility is limited by rapid clearance and potential toxicity to the central nervous system (CNS) and kidneys. To overcome these limitations, we developed a novel transdermal delivery system utilizing transfersomes loaded with majorizing Strychni semen total alkaloids (M-SSA-TFSs). Compared with conventional liposomes, M-SSA-TFSs demonstrated excellent stability, high drug encapsulation efficiency, and significantly enhanced skin permeation. Pharmacodynamic and pharmacokinetic evaluations using double-sited microdialysis confirmed that M-SSA-TFSs significantly inhibited pro-inflammatory cytokines, protected cartilage structure, and maintained sustained therapeutic drug levels in both the joint cavity and systemic circulation. Furthermore, the delivery system demonstrated favorable biocompatibility with healthy chondrocytes while exhibiting therapeutic efficacy against OA. Consequently, this study highlights M-SSA-TFSs as a superior transdermal approach that improves the dermal absorption and therapeutic index of Strychni semen, providing a valuable strategy for decelerating OA progression.

马钱子含有抗骨关节炎的生物活性总生物碱。然而，它们的应用受到快速清除和对中枢神经系统（CNS）和肾脏的潜在毒性的限制。为了克服这些限制，我们开发了一种新的透皮给药系统，利用转运体装载了马钱子总生物碱（m - ssa - tfs）。与传统脂质体相比，m - ssa - tfs具有良好的稳定性、较高的药物包封效率和显著的皮肤渗透能力。采用双位点微透析的药理学和药代动力学评估证实，m - ssa - tfs显著抑制促炎细胞因子，保护软骨结构，并在关节腔和体循环中维持持续的治疗药物水平。此外，该递送系统与健康软骨细胞表现出良好的生物相容性，同时显示出治疗OA的疗效。因此，本研究强调m - ssa - tfs是一种优越的透皮方法，可以改善马钱子精液的真皮吸收和治疗指数，为减缓OA进展提供了有价值的策略。

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引用次数: 0

A green strategy for resveratrol nanodelivery: A multidisciplinary approach for the physicochemical characterization of Thymus-based liposomes with anti-biofilm activity against Listeria monocytogenes 白藜芦醇纳米递送的绿色策略：具有抗单核增生李斯特菌生物膜活性的胸腺脂质体的理化特性的多学科方法

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.2026.108027

Maria Gioia Fabiano , Linda Maurizi , Jacopo Forte , Eleonora D'Intino , Maria Grazia Ammendolia , Davide Corinti , Astri D. Tagueha , Michela Relucenti , Orlando Donfrancesco , Federica Rinaldi , Maria Elisa Crestoni , Stefania Garzoli , Carlotta Marianecci , Maria Carafa , Catia Longhi

Nanocarrier-based drug delivery systems (DDS) offer promising strategies to enhance therapeutic efficacy, stability, and targeted delivery of bioactive compounds while reducing side effects. In this study, a multidisciplinary approach was employed to develop and characterize bioactive liposomes incorporating resveratrol (RV), a polyphenol with known therapeutic potential but limited bioavailability, and Thymus vulgaris essential oil (TEO), recognized for its antimicrobial and antioxidant properties. To obtain stable nanocarriers, liposomes were formulated using soy lecithin and prepared by thin layer evaporation technique followed by sonication process. To assess the preservation of TEO's chemical profile during formulation, Headspace Solid Phase Microextraction coupled with Gas Chromatography–Mass Spectrometry (HS-SPME/GC-MS) was performed. Quantitative analysis of thymol and carvacrol, the two main active components, was performed by HPLC-UV experiments. Physicochemical characterization of DDS was carried out employing Dynamic Light Scattering (DLS), UV–Vis spectrophotometer and Transmission electron microscopy. Antimicrobial activity was assessed by broth microdilution method, while biofilm inhibition ability was evaluated using crystal violet staining. The obtained nanocarriers exhibited appropriate physicochemical characteristics, including optimal particle size and stability. They can efficiently load both oil and RV. These features enhanced the antibacterial activity of LT-RV compared to free RV, and improved its inhibitory effect, at sub-MIC concentrations, against the sessile form of Listeria monocytogenes strains.

This study highlights the importance of integrating chemical, physical, and biological evaluations to develop effective nanocarrier-based formulations with the aim to identify a suitable strategy to combat infections associated with resistant, biofilm-producing pathogens, and offer a versatile and effective delivery platform.

基于纳米载体的药物递送系统（DDS）提供了有前途的策略，以提高治疗效果，稳定性和靶向递送的生物活性化合物，同时减少副作用。在这项研究中，采用多学科方法开发并表征了含有白藜芦醇（RV）的生物活性脂质体，白藜芦醇是一种已知具有治疗潜力但生物利用度有限的多酚，而胸腺精油（TEO）具有抗菌和抗氧化特性。为获得稳定的纳米载体，以大豆卵磷脂为原料，采用薄层蒸发-超声法制备脂质体。为了评估在制剂过程中TEO的化学特征的保存情况，采用顶空固相微萃取和气相色谱-质谱联用（HS-SPME/GC-MS）。采用HPLC-UV法对百里香酚和香芹酚两种主要活性成分进行定量分析。采用动态光散射（DLS）、紫外可见分光光度计和透射电镜对DDS进行了理化表征。采用微量肉汤稀释法测定其抑菌活性，结晶紫染色法测定其生物膜抑制能力。所制备的纳米载体具有合适的物理化学特性，包括最佳粒径和稳定性。他们可以有效地装载油和RV。与游离RV相比，这些特征增强了LT-RV的抗菌活性，并提高了其在亚mic浓度下对单核细胞增生李斯特菌的抑制作用。这项研究强调了整合化学、物理和生物学评估的重要性，以开发有效的基于纳米载体的配方，目的是确定一种合适的策略来对抗与耐药、产生生物膜的病原体相关的感染，并提供一个通用和有效的给药平台。

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引用次数: 0

CD44-targeted and pH-degradable hollow mesoporous silica nanocarriers for cancer therapy cd44靶向和ph可降解中空介孔二氧化硅纳米载体用于癌症治疗

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.2026.108045

Yi-Ching Tsai , Natesan Thirumalaivasan , Shu-Pao Wu

Targeted drug delivery systems are crucial for cancer treatment, as they boost therapeutic effectiveness while minimizing systemic toxicity. In this study, we developed pH-degradable hollow mesoporous silica nanoparticles (HMON) functionalized with hyaluronic acid (HA) for CD44-targeted drug delivery. Aryl imine organosilane was utilized to confer pH-responsiveness to the HMON, enabling controlled drug release in the mildly acidic tumor microenvironment. In vitro studies have shown that DOX@HMON-HA significantly enhances DOX uptake in CD44-overexpressing tumor cells, such as HeLa and HCT-116, leading to substantial cytotoxic effects. In contrast, CD44-low expressing cells like MCF-7 exhibit minimal DOX uptake and reduced cytotoxicity. In vivo studies further validated the therapeutic efficacy of DOX@HMON-HA, showing effective tumor growth suppression without observable systemic toxicity. These findings underscore the potential of pH-degradable hyaluronan (HA)-modified silica nanoparticles as an effective strategy for targeted cancer therapy.

靶向给药系统对癌症治疗至关重要，因为它们可以提高治疗效果，同时最大限度地减少全身毒性。在这项研究中，我们开发了ph可降解的中空介孔二氧化硅纳米颗粒（HMON），透明质酸（HA）功能化，用于cd44靶向药物递送。芳基亚胺有机硅烷被用来赋予HMON的ph响应性，从而在轻度酸性肿瘤微环境中控制药物释放。体外研究表明，DOX@HMON-HA可显著增强过表达cd44的肿瘤细胞（如HeLa和HCT-116）对DOX的摄取，从而产生显著的细胞毒性作用。相比之下，cd44低表达的细胞如MCF-7表现出最小的DOX摄取和降低的细胞毒性。体内研究进一步验证了DOX@HMON-HA的治疗效果，显示出有效的肿瘤生长抑制，没有明显的全身毒性。这些发现强调了ph可降解透明质酸修饰二氧化硅纳米颗粒作为靶向癌症治疗的有效策略的潜力。

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引用次数: 0

Intranasal calcitriol-loaded PLGA nanoparticles attenuate doxorubicin-induced cognitive impairment in rats via cGAS/STING and endoplasmic reticulum stress crosstalk 经鼻载骨化三醇的PLGA纳米颗粒通过cGAS/STING和内质网应激串扰减弱阿霉素诱导的大鼠认知功能障碍

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.2026.108019

Antoinette G. Naeem , Diana M.F. Hanna , Haidy E. Michel , Dina O. Helal , Ebtehal El-Demerdash

Doxorubicin (DOX) therapy results in cognitive impairment, known as “chemobrain”. Calcitriol (CAL) confers neuroprotection in many neuropathologies. Our objective was to develop a nose-to-brain nanocarrier-based delivery system of CAL for enhanced brain targeting and efficacy. CAL was loaded in poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) using the nanoprecipitation technique. Effects of formulation parameters on NPs physicochemical properties were evaluated. The neuroprotective effect of oral CAL solution (100 ng/kg/day) or intranasal CAL solution or CAL-NPs (30 ng/kg/day) was assessed in DOX-induced chemobrain rat model by neurobehavioral, histopathological, and biochemical assessments. CAL-NPs composed of 10 mg PLGA, 0.1 % Tween® 80 and 30 μg CAL were optimum for nose-to-brain delivery with particle size, polydispersity index, zeta potential, and entrapment efficiency of 164 ± 5.47 nm, 0.18 ± 0.02, −18.3 ± 0.6 mV, and 51.39 ± 1.53 %, respectively. Transmission electron microscope imaging confirmed the formation of spherical particles, and in vitro drug release showed a biphasic pattern with sustained drug release up to one week. Intranasal CAL treatment enhanced cognition, restored hippocampal histoarchitecture, and suppressed acetylcholinesterase activity. CAL hindered hippocampal neuroinflammation by enhancing sirtuin (SIRT) 1 expression and mitigating the cGAS/STING/p-TBK-1/NF-κB p65 axis and its effector cytokines. In addition, it suppressed p-IRE-1α/XBP-1s endoplasmic reticulum stress axis and its downstream pro-apoptotic CCAAT/enhancer binding protein homologous (CHOP) and caspase-3. Collectively, intranasal administration of CAL, particularly via PLGA NPs, enhanced CAL neuroprotective effect at one-third the oral dose, suggesting the potential use of CAL-NPs as a promising nose-to-brain delivery system for mitigation of DOX-induced chemobrain.

阿霉素（DOX）治疗导致认知障碍，被称为“化学脑”。骨化三醇（CAL）在许多神经病变中具有神经保护作用。我们的目标是开发一种基于鼻子到大脑的纳米载体给药系统，以增强大脑靶向性和有效性。采用纳米沉淀法将CAL负载于聚乳酸-羟基乙酸（PLGA）纳米颗粒（NPs）中。考察了配方参数对NPs理化性质的影响。在dox诱导的化学脑大鼠模型中，通过神经行为学、组织病理学和生物化学评估评估口服CAL溶液（100 ng/kg/day）或鼻内CAL溶液或CAL- nps （30 ng/kg/day）的神经保护作用。CAL- nps由10 mg PLGA、0.1% Tween®80和30 μg CAL组成，其粒径、多分散指数、zeta电位和包封效率分别为164±5.47 nm、0.18±0.02、- 18.3±0.6 mV和51.39±1.53%，最适合经鼻至脑传递。透射电镜成像证实形成球形颗粒，体外释药呈双相模式，持续释药时间长达一周。鼻内CAL治疗增强认知，恢复海马组织结构，抑制乙酰胆碱酯酶活性。CAL通过提高sirtuin (SIRT) 1的表达，减轻cGAS/STING/p-TBK-1/NF-κB p65轴及其效应细胞因子，抑制海马神经炎症。此外，它还能抑制p-IRE-1α/ xbp -1内质网应激轴及其下游促凋亡的CCAAT/增强子结合蛋白同源体（CHOP）和caspase-3。总的来说，CAL经鼻给药，特别是通过PLGA NPs， CAL的神经保护作用增强了口服剂量的三分之一，这表明CAL-NPs有可能作为一种有前途的鼻子到大脑的给药系统来缓解dox诱导的化学脑。

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引用次数: 0

Development and characterization of orally disintegrating films of Nebivolol as complex with Sulfobutylether-β-cyclodextrin 奈比洛尔与磺基丁醚-β-环糊精配合物口腔崩解膜的研制与表征

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.2026.108043

Marzia Cirri , Silvia Fiani , Francesca Maestrelli , Natascia Mennini , Maria Cristina Salvatici , Paola Mura

Low water solubility and extensive hepatic first-pass metabolism limit oral bioavailability of Nebivolol hydrochloride (NEB), a new-generation β-blocker agent effective in hypertension treatment. To overcome such issues, a combined strategy was applied, based on the development of orally disintegrating films (ODFs) loaded with NEB as SBEβCD complex. This approach exploits both the SBEβCD solubilizing power and the fast drug dissolution in the oral cavity provided by ODF. Preformulation studies allowed to select the best combinations of film-forming polymers (PVA in mixture with Na alginate or HPMC) and plasticizer (PEG 400) to obtain ODFs with the desired properties. Loading of selected ODF formulations with NEB-SBEβCD complex significantly increased its dissolution rate: >50 % drug dissolved in simulated saliva after 5′ and 100 % in simulated gastric medium within 30’. In contrast, the plain drug achieved only 30 % and 70 % dissolution, respectively.

This should enhance the drug fraction absorbed in the pre-gastric tract, limiting hepatic first-pass metabolism. Moreover, SBEβCD caused a significant reduction of the film disintegration time, due to the higher water-affinity of the drug-CD complex than free drug. Finally, the drug entrapment within the CD cavity should prevent palatability problems related to drug bitter taste, avoiding addition of flavoring agents.

盐酸奈比洛尔（Nebivolol hydrochloride， NEB）是一种有效治疗高血压的新一代β受体阻滞剂，其低水溶性和广泛的肝脏首过代谢限制了其口服生物利用度。为了克服这些问题，采用了一种基于口腔崩解膜（odf）的综合策略，该膜负载NEB作为sbe - β - cd复合物。该方法利用了ODF在口腔内的快速药物溶解能力和sbe β - cd的溶解能力。预配方研究允许选择成膜聚合物（PVA与海藻酸钠或HPMC混合）和增塑剂（PEG 400）的最佳组合，以获得具有所需性能的odf。在选定的ODF制剂中加入neb - sheb β - cd配合物可显著提高其溶出率：5 ‘后药物在模拟唾液中溶出50%，30 ’内药物在模拟胃介质中溶出100%。相比之下，普通药物分别只有30%和70%的溶出度。这将增强胃前道吸收的药物部分，限制肝脏第一次代谢。此外，由于药物- cd复合物比游离药物具有更高的水亲和性，SBEβCD显著缩短了膜崩解时间。最后，药物在CD腔内的包裹应防止与药物苦味有关的适口性问题，避免添加调味剂。

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引用次数: 0

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