Journal of Drug Delivery Science and Technology最新文献_第7页

Why protransfersome nanovesicles are a game-changer in drug delivery? An overview and future vision 为什么蛋白质转移纳米囊泡会改变药物传递的游戏规则？概述和未来展望

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-22 DOI: 10.1016/j.jddst.2025.107947

Mohamed A. Akl

Transdermal Drug Delivery (TDD) offers a superior alternative to oral routes by providing controlled release and enhanced patient compliance. By delivering drugs directly across the skin, TDD preserves the integrity of sensitive molecules by bypassing the gastrointestinal tract, avoiding acid-catalyzed hydrolysis and proteolytic cleavage by intestinal enzymes. Furthermore, this route circumvents first-pass hepatic metabolism, preventing the rapid enzymatic degradation and pH-related instability that often limit the bioavailability of lipophilic and macromolecular drugs. Consequently, TDD ensures higher therapeutic integrity and consistent systemic absorption compared to oral delivery. Despite these benefits, the Stratum Corneum (SC) remains a formidable barrier, particularly against large or charged molecules. While chemical and physical enhancers are used to improve flux, they are often limited by skin toxicity or high cost. To address these challenges, Transfersomes (TF)—highly deformable lipid vesicles—have emerged as effective carriers for deep skin penetration. These advanced lipid-based carriers build upon the limitations of traditional liposomes, which suffer from inherent physical instability that complicates storage and application. To address this, Protransfersomes (PTF) were introduced as stable, provesicular precursors that, upon contact with epidermal moisture, undergo an in situ hydration mechanism to transform into ultraflexible TF. Driven by the trans-epidermal osmotic gradient, these vesicles deform to navigate narrow intercellular channels, significantly enhancing drug transport. This review provides a comprehensive analysis of PTF as a novel provesicular system, offering insights into their design, mechanisms of action, and fabrication techniques. Furthermore, it evaluates critical quality attributes, including mean Particle Size (PS), Entrapment Efficiency (EE), turbidity, and stability, highlighting the translational potential of PTF as a robust platform for next-generation drug delivery.

经皮给药（TDD）提供了更好的替代口服途径，提供控制释放和提高患者的依从性。通过直接通过皮肤递送药物，TDD绕过胃肠道，保持敏感分子的完整性，避免了肠道酶的酸催化水解和蛋白水解裂解。此外，这一途径绕过了第一次肝脏代谢，阻止了快速的酶降解和ph相关的不稳定性，而这些通常限制了亲脂性和大分子药物的生物利用度。因此，与口服给药相比，TDD可确保更高的治疗完整性和一致的全身吸收。尽管有这些好处，角质层（SC）仍然是一个强大的屏障，特别是对大分子或带电分子。虽然使用化学和物理增强剂来改善通量，但它们往往受到皮肤毒性或高成本的限制。为了解决这些挑战，转移体(TF) -高度可变形的脂质囊-已经成为深入皮肤渗透的有效载体。这些先进的基于脂质的载体建立在传统脂质体的局限性之上，传统脂质体遭受固有的物理不稳定性，使储存和应用复杂化。为了解决这一问题，原转移体（PTF）作为稳定的前体被引入，当与表皮水分接触时，经过原位水化机制转化为超柔性TF。在跨表皮渗透梯度的驱动下，这些囊泡变形以通过狭窄的细胞间通道，显著增强药物运输。这篇综述提供了PTF作为一种新颖的暂态系统的全面分析，提供了他们的设计，作用机制和制造技术的见解。此外，它还评估了关键的质量属性，包括平均粒径（PS）、捕获效率（EE）、浊度和稳定性，突出了PTF作为下一代药物输送平台的转化潜力。

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引用次数: 0

Buccal gelatin film of active pharmaceutical ingredient-ionic liquid: Incorporation of oil emulsion to improve the film's physical attributes and stability 活性药物成分-离子液体口腔明胶膜：加入油乳剂改善膜的物理性质和稳定性

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-19 DOI: 10.1016/j.jddst.2025.107942

Liu Han Ng, Arnav Gupta, Siyu Pu, Kunn Hadinoto

Formulating poorly-soluble active pharmaceutical ingredients (API) into their ionic liquid (IL) salts can simultaneously enhance API solubility and avoid polymorphic conversion of the API. Previously, we developed API-IL-loaded gelatin films intended for buccal delivery using ibuprofen (IBU) as the model poorly-soluble drug with 1-butyl-3-methylimidazolium (BMIM) as counterion. The gelatin films, however, exhibited poor physical stability due to gelatin aggregation during storage. This study aimed to improve the physical stability of IBU-BMIM-loaded gelatin films by incorporating olive oil emulsion. First, we investigated the effects of oil inclusion at different oil contents (3.2–20 wt %) on the films' (i) IBU-BMIM payload and payload uniformity, (ii) folding endurance, (iii) weight/thickness variations, (iv) water vapor permeability, (v) IBU-BMIM release and IBU kinetic solubility. Subsequently, the films' physical stability after three months of accelerated storage was evaluated, while their chemical stability will be assessed in a future study. Oil inclusion did not affect the physical form of IBU-BMIM in the films as the oil remained physically dispersed in the films without forming molecular interactions with gelatin or IBU-BMIM. Oil inclusion below 10 wt% improved the films' folding endurance, thickness, water vapor permeability, IBU-BMIM release, and IBU kinetic solubility, with minimal impacts on IBU-BMIM payload and film weight. Excessive oil contents, however, led to poor IBU-BMIM payload uniformity. Oil inclusion prevented gelatin aggregation during storage as the immiscible oil phase suppressed the gelatin's polymer chain mobility. Consequently, minimal changes in the films' physical attributes were observed after storage.

将难溶性活性药物成分（API）配制成其离子液体（IL）盐，可以同时提高API的溶解度，避免API的多态转化。此前，我们以布洛芬（IBU）为模型难溶性药物，以1-丁基-3-甲基咪唑（BMIM）为对抗剂，开发了用于口腔给药的api - il负载明胶薄膜。然而，由于明胶在储存过程中聚集，明胶薄膜表现出较差的物理稳定性。本研究旨在通过加入橄榄油乳剂来提高ibu - bmim负载明胶薄膜的物理稳定性。首先，我们研究了不同含油量（3.2-20 wt %）下包裹油对薄膜(i) IBU- bmim有效载荷和有效载荷均匀性、（ii）折叠耐久性、（iii）重量/厚度变化、（iv）水蒸气渗透性、(v) IBU- bmim释放和IBU动力学溶解度的影响。随后，在三个月的加速储存后，对薄膜的物理稳定性进行了评估，而其化学稳定性将在未来的研究中进行评估。油包裹并不影响IBU-BMIM在膜中的物理形态，因为油在膜中保持物理分散，不会与明胶或IBU-BMIM形成分子相互作用。10% wt以下的油包裹体提高了膜的折叠耐久性、厚度、水蒸气渗透率、IBU- bmim释放量和IBU动力学溶解度，对IBU- bmim有效载荷和膜重的影响最小。然而，含油量过高导致IBU-BMIM有效载荷均匀性差。由于不混相的油相抑制了明胶的聚合物链流动性，因此油包合物阻止了明胶在储存过程中的聚集。因此，在储存后，观察到薄膜物理属性的最小变化。

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引用次数: 0

Reactive oxygen species-responsive hyaluronic acid-b-PEG copolymer nanoparticles for doxorubicin delivery and therapeutic efficacy in oral squamous cell carcinoma 活性氧反应透明质酸-b- peg共聚物纳米颗粒用于阿霉素在口腔鳞状细胞癌中的传递和治疗效果

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-18 DOI: 10.1016/j.jddst.2025.107938

Inho Bae , Hee Jung Kim , Byung-Hoon Kim

Reactive oxygen species (ROS)-responsive nanocarriers represent an emerging strategy for tumor-targeted drug delivery. Herein, we synthesized a hyaluronic acid (HA)-b-poly(ethylene glycol) (PEG) copolymer incorporating a ROS-labile PBAP linker, designed for controlled release of doxorubicin (DOX) under oxidative stress. The amphiphilic HA(PBAP)-b-PEG copolymer self-assembled into nanoparticles with a mean diameter of 138.4 ± 14.8 nm, exhibiting spherical morphology as observed by transmission electron microscopy. DOX was incorporated into nanoparticles via ionic complexation and hydrophobic interactions, resulting in high encapsulation efficiency. In vitro drug release studies revealed sustained DOX release under physiological conditions, with markedly accelerated release in the presence of hydrogen peroxide. Cellular uptake analysis showed enhanced intracellular accumulation of DOX delivered by nanoparticles compared with free DOX in AT84 oral squamous carcinoma cells. Cytotoxicity assays confirmed superior anticancer activity of DOX-loaded nanoparticles, particularly under oxidative conditions. Apoptosis/necrosis analysis further demonstrated ROS-dependent cell death. Collectively, these findings highlight the potential of HA(PBAP)-b-PEG copolymer nanoparticles as a promising nanoplatform for ROS-triggered, tumor-targeted chemotherapy in oral cancer.

活性氧（ROS）反应的纳米载体代表了一种新兴的肿瘤靶向药物递送策略。在此，我们合成了一种透明质酸(HA)-b-聚乙二醇（PEG）共聚物，该共聚物含有ros -不稳定的ppbap连接剂，旨在氧化应激下控制阿霉素（DOX）的释放。两亲性HA(PBAP)-b-PEG共聚物自组装成平均直径为138.4±14.8 nm的纳米颗粒，透射电镜观察到其形貌为球形。DOX通过离子络合和疏水相互作用结合到纳米颗粒中，具有较高的包封效率。体外药物释放研究显示，DOX在生理条件下持续释放，在过氧化氢存在下明显加速释放。细胞摄取分析显示，与游离DOX相比，纳米颗粒在AT84口腔鳞癌细胞内的蓄积增强。细胞毒性试验证实了负载dox的纳米颗粒具有优异的抗癌活性，特别是在氧化条件下。凋亡/坏死分析进一步证实ros依赖性细胞死亡。总的来说，这些发现突出了HA(PBAP)-b-PEG共聚物纳米颗粒作为ros触发的口腔癌肿瘤靶向化疗的有前途的纳米平台的潜力。

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引用次数: 0

Liposomal co-delivery of luteolin and piperine for enhanced lung cancer cell death: in vitro characterization, biosafety and anticancer activity 木犀草素和胡椒碱脂质体共同递送促进肺癌细胞死亡：体外表征、生物安全性和抗癌活性

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-18 DOI: 10.1016/j.jddst.2025.107940

Riyad F. Alzhrani , Syed Sarim Imam , Sultan Alshehri , Mohammed Mufadhe Alanazi , Wael Mahdi , Rawan A. Fitaihi , Saad Alobid , Gamaleldin I. Harisa

Chemotherapy is the primary therapeutic approach for different kinds of cancers; however, its clinical effectiveness is often limited by systemic toxicity and adverse side effects. In the present study, we developed a liposomal vesicular system to deliver two lipophilic natural anticancer compounds, Luteolin and Piperine, to enhance their therapeutic activity. The liposomes were prepared using the solvent evaporation method with various non-ionic surfactants. Comprehensive physicochemical characterization was performed for the prepared liposomes including measurements of physical characterizations, encapsulation efficiency and Infrared spectroscopy. The mechanism of luteolin and piperine release was assessed using various kinetic models. The in vitro anticancer efficacy of drug-loaded liposomes against A549 human lung cancer cells (cell viability, apoptosis, reactive oxygen species and cell migration) was also assessed. The drug-loaded liposomes exhibited nano-metric size (183 ± 4.8 to 198 ± 5.3 nm), and negative zeta potential (−17.8 ± 3.1 to −23 ± 2.7 mV). The analysis of the liposomal content revealed higher encapsulation of luteolin (75.4 ± 3.1 to 82.7 ± 3.4 %) and piperine (79.9 ± 3.2 to 86.7 ± 3.2 %). The drug release study exhibited a prolonged release behavior for luteolin and piperine, with cumulative releases of 61.2 ± 2.9 % and 73.6 ± 3.7 %, respectively. The prepared liposomes co-loaded with luteolin and piperine have demonstrated high toxicity to lung cancer cells, which was confirmed by a significant reduction in IC₅₀ of 3.12 and 12.5 μM, for Luteolin and Piperine, respectively. The biocompatibility study findings depicted a safe formulation with no hemolysis observed. The apoptosis and cell migration result also suggest that a significantly high percentage of cells shifted to late apoptosis and exhibited a reduced migratory effect. Overall, the co-loading of luteolin and piperine in liposomes offers an effective therapeutic strategy for the treatment of lung cancer and sets the stage for a comprehensive evaluation of its pharmacokinetics, safety and efficacy in a murine model.

化疗是不同类型癌症的主要治疗方法；然而，其临床效果往往受到全身毒性和不良副作用的限制。在本研究中，我们开发了一种脂质体囊泡系统，以输送两种亲脂性天然抗癌化合物木犀草素和胡椒碱，以增强其治疗活性。采用溶剂蒸发法制备脂质体，并加入多种非离子表面活性剂。对制备的脂质体进行了全面的理化表征，包括物理表征、包封效率和红外光谱测量。采用多种动力学模型对木犀草素和胡椒碱的释放机制进行了评价。研究了载药脂质体对A549人肺癌细胞的体外抗癌作用（细胞活力、细胞凋亡、活性氧和细胞迁移）。载药脂质体具有纳米级尺寸（183±4.8 ~ 198±5.3 nm）和负zeta电位（−17.8±3.1 ~−23±2.7 mV）。脂质体含量分析显示木犀草素（75.4±3.1 ~ 82.7±3.4 %）和胡椒碱（79.9±3.2 ~ 86.7±3.2 %）的包封率较高。药物释放研究显示木犀草素和胡椒碱具有缓释行为，累积释放量分别为61.2±2.9%和73.6±3.7%。所制备的木犀草素和胡椒碱共载脂质体对肺癌细胞具有高毒性，木犀草素和胡椒碱的IC50分别显著降低3.12 μM和12.5 μM。生物相容性研究结果描述了一种安全的配方，没有观察到溶血。细胞凋亡和细胞迁移结果也表明，细胞转移到晚期凋亡的比例明显较高，迁移作用减弱。总之，木犀草素和胡椒碱在脂质体中的共载为治疗肺癌提供了一种有效的治疗策略，并为其在小鼠模型中的药代动力学、安全性和有效性的综合评估奠定了基础。

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引用次数: 0

From bench to bedside: Three-dimensional (3D) printing of pediatric dosage forms for personalized pharmacotherapy 从工作台到床边：用于个性化药物治疗的儿科剂型的三维（3D）打印

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-18 DOI: 10.1016/j.jddst.2025.107939

Awaji Y. Safhi

Three-dimensional (3D) printing has emerged as a transformative technology in pediatric drug delivery, offering solutions to long-standing challenges such as dose flexibility, palatability, swallowability, and adherence. Conventional pharmaceutical manufacturing often fails to meet these needs due to its reliance on standardized, adult-oriented dosage forms. In contrast, 3D printing techniques including inkjet printing, fused deposition modeling (FDM), semi-solid extrusion (SSE), selective laser sintering (SLS), and stereolithography (SLA) enable the fabrication of personalized, child-friendly formulations with precise dosing, customizable geometries, and tailored drug release profiles. Research has demonstrated the feasibility of producing orodispersible tablets (ODTs), chewable gummies, mini-tablets, and chocolate or gummy-based dosage forms that enhance acceptance and compliance. Preclinical and clinical evaluations show that 3D-printed formulations can achieve pharmacokinetic bioequivalence, more than 80 % rapid drug release, and compliance with pharmacopeial quality standards, while also improving taste masking and caregiver usability. Early translational studies, such as personalized chewable printlets for metabolic disorders, highlight the clinical promise of this approach. Nevertheless, challenges remain in scalability, reproducibility, excipient validation for children, long-term stability, cost-effectiveness, and regulatory harmonization. Ethical and legal issues surrounding liability and data governance must also be addressed. Overall, 3D printing represents a paradigm shift toward personalized, patient-centric pediatric pharmacotherapy, bridging therapeutic efficacy with improved adherence and quality of life. This review, based on the recent literature, aims to critically evaluate the opportunities and challenges associated with utilizing 3D printing technologies to pediatric medicine, emphasizing their potential to advance personalized and patient friendly therapies.

三维（3D）打印已经成为儿科给药领域的一项变革性技术，为长期存在的挑战提供了解决方案，如剂量灵活性、适口性、可吞性和依从性。传统的药品生产往往不能满足这些需求，因为它依赖于标准化的、面向成人的剂型。相比之下，3D打印技术，包括喷墨打印、熔融沉积建模（FDM）、半固体挤压（SSE）、选择性激光烧结（SLS）和立体光刻（SLA），能够制造出个性化的、适合儿童的配方，具有精确的剂量、可定制的几何形状和量身定制的药物释放曲线。研究已经证明了生产口服分散片（ODTs）、咀嚼软糖、迷你片和巧克力或软糖剂型的可行性，这些剂型可以提高接受度和依从性。临床前和临床评估表明，3d打印制剂可以实现药代动力学生物等效性，80%以上的药物快速释放，符合药典质量标准，同时还可以改善味道掩蔽和护理人员的可用性。早期的转化研究，如针对代谢紊乱的个性化可咀嚼小片，突出了这种方法的临床前景。然而，在可扩展性、可重复性、儿童赋形剂验证、长期稳定性、成本效益和监管协调方面仍然存在挑战。还必须解决有关责任和数据治理的道德和法律问题。总的来说，3D打印代表了一种向个性化、以患者为中心的儿科药物治疗的范式转变，将治疗效果与改善的依从性和生活质量联系起来。本综述基于最近的文献，旨在批判性地评估将3D打印技术应用于儿科医学的机遇和挑战，强调其在推进个性化和患者友好治疗方面的潜力。

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引用次数: 0

Designing a lyophilization cycle for albumin-bound pioglitazone nanoparticles through the utilization of analytical and simulation tools, along with conventional monitoring parameters 利用分析和模拟工具，结合常规监测参数，设计白蛋白结合吡格列酮纳米颗粒的冻干循环

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-17 DOI: 10.1016/j.jddst.2025.107934

Saswata Banerjee , Gautam Singhvi , Rajeev Taliyan , Ajay Kumar Bachupally

引用次数: 0

Exploring the treatment potential of traditional Chinese medicine-loaded nano transferosomal gel in osteoporosis induced rats 探讨中药纳米转移体凝胶对骨质疏松大鼠的治疗潜力

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-17 DOI: 10.1016/j.jddst.2025.107926

Yunfeng Ma , Omer Mustapha , Shumaila Shafique , Xiaofei Han , Haroon Ahmed , Zakir Ali , Fakhar ud Din

This study aims to develop and investigate the treatment potential of Morinda Root Extract (MRE) loaded nanogel in ovariectomy (OVX)-induced osteoporosis (OVX-OP). MRE has limited therapeutic efficacy due to poor solubility and limited permeability. Thus, MRE-loaded nano transfersomes (MRE-NT) were prepared and characterized for vesicles properties including mean particle size, PDI and zeta potential. Entrapment efficiency (EE) and morphology of the developed MRE-NT were investigated. Moreover, the MRE-NT was further loaded into chitosan gel to prepare MRE-NTG, which was subjected to rheological investigations including, viscosity, spread-ability pH, and homogeneity. In vitro release profiles of the MRE-NTG and MRE conventional gel were accomplished followed by ex vivo analysis. Bioavailability of the prepared MRE-NTG was investigated in Sprague-Dawley rats and compared with MRE conventional gel. Furthermore, anti-OP effects of the MRE-NTG were examined in OVX-OP rats by evaluating serum and urine biomarkers. MRE-NT exhibited vesicles in nano size range (175.7 nm) with suitable PDI (0.171), zeta potential (12.1 mV) and %EE (96 %). Moreover, the vesicles were rounded in shape and morphology. The MRE-NTG exhibited suitable viscosity 29844 cp, pH 5.51, uniformity and spread ability. A significantly improved release of MRE was observed at pH 7.4 as compared with pH 5.5. Moreover, MRE-NTG showed improved in vitro release and cumulative permeated amount of MRE when compared with conventional gel. Additionally, a 6-fold enhanced bioavailability of MRE was observed in MRE-NTG treated rats. Furthermore, an improved anti-OP effect of the prepared NTG was observed in Sprague-Dawley rats with reduced levels of serum and urine biomarkers. This study concluded an enhanced efficacy of the traditional Chinese medicine, after incorporation in nanogel, in the treatment of OP.

本研究旨在开发和研究负载莫林根提取物（MRE）纳米凝胶在卵巢切除术（OVX）所致骨质疏松症（OVX- op）中的治疗潜力。由于溶解度差、渗透性有限，MRE的治疗效果有限。因此，制备了负载mre的纳米转移体（MRE-NT），并对其进行了囊泡性质的表征，包括平均粒径、PDI和zeta电位。研究了开发后的MRE-NT的捕集效率（EE）和形貌。此外，将MRE-NT进一步装入壳聚糖凝胶中制备MRE-NTG，并对其进行了流变学研究，包括粘度、铺展性、pH和均匀性。完成了MRE- ntg和MRE常规凝胶的体外释放谱，并进行了离体分析。研究制备的MRE- ntg在大鼠体内的生物利用度，并与MRE常规凝胶进行比较。此外，通过评估OVX-OP大鼠的血清和尿液生物标志物，研究了MRE-NTG的抗op作用。MRE-NT在纳米尺度（175.7 nm）范围内具有合适的PDI（0.171）、zeta电位（12.1 mV）和EE（96%）。此外，囊泡在形状和形态上呈圆形。MRE-NTG的黏度为29844 cp， pH值为5.51，均匀性好，涂抹能力强。与pH为5.5相比，pH为7.4时MRE的释放明显改善。此外，与常规凝胶相比，MRE- ntg的体外释放和MRE的累积渗透量均有所改善。此外，在MRE- ntg治疗的大鼠中观察到MRE的生物利用度提高了6倍。此外，在Sprague-Dawley大鼠血清和尿液生物标志物水平降低的情况下，观察到制备的NTG具有改善的抗op作用。本研究表明，中药掺入纳米凝胶后，对OP的治疗效果明显增强。

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引用次数: 0

Targeted delivery of RNA using synthetic bacterial spores 利用合成细菌孢子靶向递送RNA

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-17 DOI: 10.1016/j.jddst.2025.107933

Federico Machinandiarena , Domenico D'Atri , Lisa M. Jenkins , Kandice Tanner , David J. Fitzgerald , Kumaran S. Ramamurthi

RNA therapy, which includes delivery of mRNA or siRNA, shows promise for treating various diseases, but difficulties in targeting specific cell types and low efficiency of loading RNA into nanoparticles remain hurdles to achieving widespread use. Previously, we reported the assembly of biocompatible synthetic bacterial spore-like particles, termed “SSHELs”, which are built atop a porous silica core encased in a lipid bilayer and two bacterial proteins that form a stable proteinaceous surface that may be covalently modified with targeting proteins of interest. Here, we employ micron-scale SSHELs constructed using a fusogenic lipid and decorated with affibodies targeting cell surface HER2 to specifically deliver model mRNA and siRNA molecules specifically to HER2-positive ovarian and breast cancer cells, with high RNA loading efficiency and cargo capacity. SSHEL particles therefore represent a versatile vehicle for the delivery of not only small molecules, but also therapeutic RNA to specific cell types.

RNA疗法，包括mRNA或siRNA的递送，显示出治疗多种疾病的希望，但靶向特定细胞类型的困难和将RNA装载到纳米颗粒中的低效率仍然是实现广泛应用的障碍。之前，我们报道了生物相容性合成细菌孢子样颗粒的组装，称为“SSHELs”，其构建在被脂质双分子层包裹的多孔二氧化硅核上，两种细菌蛋白形成稳定的蛋白表面，可以与感兴趣的靶向蛋白共价修饰。在这里，我们使用微米尺度的SSHELs构建了一种融合性脂质，并装饰了靶向细胞表面HER2的修饰物，特异性地将模型mRNA和siRNA分子特异性地递送到HER2阳性的卵巢癌和乳腺癌细胞，具有高RNA装载效率和载重量。因此，SSHEL颗粒代表了一种多功能载体，不仅可以将小分子递送，还可以将治疗性RNA递送到特定的细胞类型。

引用次数: 0

Tofacitinib citrate loaded perillyl alcohol enriched functional nanostructured lipid carriers gel boosted re-pigmentation in vitiligo: Immunohistochemical, protein, and mRNA expression analysis 负载枸橼酸托法替尼的紫苏醇富集功能纳米结构脂质载体凝胶促进白癜风的再着色：免疫组织化学、蛋白质和mRNA表达分析

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-16 DOI: 10.1016/j.jddst.2025.107936

Harithasree Veerabomma , Saptarshee Bhattacharjee , Siva Singothu , Jitendra Kumar , Divyasree Vulli , Vasundhra Bhandari , Jitender Madan

Vitiligo is a chronic autoimmune skin disease characterized by the selective destruction of melanocytes, resulting in depigmented macules and patches. Tofacitinib citrate (TC), a Janus kinase 1/3 (JAK1/3) inhibitor, has emerged as a capable therapeutic agent for vitiligo therapy; however, its oral administration is associated with systemic side effects. Therefore, in the present investigation, tofacitinib citrate-loaded functional nanostructured lipid carriers (TC-F-NLCs) enriched with perillyl alcohol were scaled up using the hot emulsification technique under the framework of face-centered central composite design. Next, TC-F-NLCs were assessed for particle size (133.8 ± 1.99 nm), polydispersity index (PDI; 0.219 ± 0.008), zeta (ζ) potential (−29.6 ± 1.17 mV), entrapment efficiency (89.2 ± 0.03 %), and surface topography. Later, TC-F-NLCs were transformed into tofacitinib citrate-loaded functional nanostructured lipid carriers amalgamated gel (TC-F-NLCs-Gel). TC-F-NLCs-Gel demonstrated a 4.4-fold increment in skin deposition compared to conventional tofacitinib citrate ointment. The therapeutic efficacy of TC-F-NLCs-Gel was assessed in validated experimental vitiligo induced by 40 % w/w monobenzone ointment in C57BL/6 male mice. TC-F-NLCs-Gel revealed enhanced melanogenic potential through elevated melanin synthesis, along with diminished reactive oxygen species (ROS) and nitric oxide (NoX) levels. Moreover, TC-F-NLCs-Gel also suppressed pro-inflammatory cytokine mRNA expressions (JAK1, JAK3, IL-6, IFN-γ, and IL-1β) in experimental vitiligo significantly (One-way ANOVA test, ^###P < 0.001), higher than functional nanostructured lipid carriers enriched with perillyl alcohol amalgamated gel (F-NLCs-Gel) used as a placebo. Thus, the additive efficacy offered by TC-F-NLCs-Gel enriched with perillyl alcohol in promoting re-pigmentation in experimental vitiligo may be attributed to the inhibition of the JAK/STAT pathway, in addition to the attenuation of oxidative stress markers. Hence, TC-F-NLCs-Gel may be a potential candidate for translating into a clinically viable nanopharmaceutical product.

白癜风是一种慢性自身免疫性皮肤病，其特征是黑色素细胞的选择性破坏，导致脱色斑和斑块。柠檬酸托法替尼（TC）是一种Janus激酶1/3 （JAK1/3）抑制剂，已成为白癜风治疗的有效药物；然而，其口服给药与全身副作用有关。因此，本研究在面心中心复合设计的框架下，采用热乳化技术放大了富含紫苏醇的负载柠檬酸托法替尼的功能纳米结构脂质载体（tc - f - nlc）。接下来，评估tc - f - nlc的粒径（133.8±1.99 nm），多分散性指数（PDI; 0.219±0.008），ζ (ζ)电位（- 29.6±1.17 mV），捕获效率（89.2±0.03%）和表面形貌。随后，将tc - f - nlc转化为负载柠檬酸托法替尼的功能纳米结构脂质载体合并凝胶（tc - f - nlc - gel）。与传统的柠檬酸托法替尼软膏相比，tc -f - nlc -凝胶显示皮肤沉积增加4.4倍。研究了tc - f - nlc -凝胶对C57BL/6雄性小鼠实验性白癜风的治疗效果。tc - f - nlc - gel显示，通过提高黑色素合成，降低活性氧（ROS）和一氧化氮（NoX）水平，增强了黑色素生成潜力。此外，tc - f - nlc - gel还显著抑制实验性白癜风中促炎细胞因子mRNA （JAK1, JAK3, IL-6， IFN-γ和IL-1β）的表达（单因素方差分析，0.001），高于功能纳米结构脂质载体紫叶醇混合凝胶（f - nlc - gel）作为安慰剂。因此，富含紫杉醇的tc - f - nlc - gel在促进实验性白癜风再着色方面的加性作用，除了可以抑制氧化应激标志物外，还可以抑制JAK/STAT通路。因此，tc - f - nlc - gel可能是转化为临床可行的纳米药物产品的潜在候选者。

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引用次数: 0

Sr-doped mesoporous silica nanoparticles with enhanced biological functions and 3D printing applications 具有增强生物功能的sr掺杂介孔二氧化硅纳米颗粒及其3D打印应用

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-16 DOI: 10.1016/j.jddst.2025.107932

Bhuvan Bhaskar Tripathi , Reena Yadav , Ananya Aeri , Vinod Kumar , G. Taru Sharma

The development of multifunctional biomaterials that can be able to simultaneously promote stem cell differentiation, vascularization, and antimicrobial activity has long been a major hurdle in the field of regenerative medicine. In this study, we report the development and extensive biological characteristics of Strontium-doped mesoporous silica nanoparticles (Sr-MSNs) as a versatile platform for bone tissue regeneration. Sr-MSNs were synthesized by a modified Stöber method and followed by thorough characterization through various microscopic and spectroscopic tools. The Sr-MSNs exhibited a well-organized mesoporous framework endowed with extensive crystallinity and surface area for efficient ion exchange and bioactivity. Sr-MSNs showed high biocompatibility and revealed negligible cell toxicity and no disruption in cell cycle progression, and were easily internalized by caprine amniotic membrane-derived mesenchymal stem cells (cAMSCs). Remarkably, Sr-MSNs significantly improved the trilineage differentiation of cAMSCs towards the osteogenic, chondrogenic, and adipogenic lineages, highlighting their intrinsic capability to modulate the fate of stem cells. Furthermore, Sr-MSNs stimulated angiogenic responses by a chick chorio-allantoic membrane assay and also exhibited a wide range of antibacterial activity against Escherichia coli and Staphylococcus aureus. Increased apatite deposition in simulated body fluid indicates their enhanced biomineralization potential. Integration of Sr-MSNs into 3D-printed Xanthan gum scaffolds resulted in hybrid constructs with excellent cytocompatibility and structural stability. The combination of their commendable trilineage differentiation features, pro-angiogenic, and antibacterial capabilities validates the multifunctional nature of Sr-MSNs, making them promising candidates for the new generation of bioactive scaffolds and complex bone tissue regeneration scaffolds.

开发能够同时促进干细胞分化、血管形成和抗菌活性的多功能生物材料一直是再生医学领域的主要障碍。在这项研究中，我们报道了锶掺杂介孔二氧化硅纳米颗粒（Sr-MSNs）作为骨组织再生的通用平台的发展和广泛的生物学特性。Sr-MSNs是通过一种改进的Stöber方法合成的，然后通过各种显微镜和光谱工具进行了全面的表征。sr - msn表现出组织良好的介孔结构，具有广泛的结晶度和表面积，具有高效的离子交换和生物活性。Sr-MSNs具有很高的生物相容性，细胞毒性很小，不破坏细胞周期进程，易于被羊膜源间充质干细胞（cAMSCs）内化。值得注意的是，sr - msn显著改善了cAMSCs向成骨、软骨和脂肪谱系的三期分化，突出了它们调节干细胞命运的内在能力。此外，通过鸡绒毛膜-尿囊膜试验，Sr-MSNs刺激血管生成反应，并对大肠杆菌和金黄色葡萄球菌表现出广泛的抗菌活性。模拟体液中磷灰石沉积增加表明其生物矿化潜力增强。将sr - msn整合到3d打印的黄原胶支架中，产生了具有优异细胞相容性和结构稳定性的杂交结构。其令人称赞的三期分化特征、促血管生成和抗菌能力的结合验证了sr - msn的多功能特性，使其成为新一代生物活性支架和复杂骨组织再生支架的有希望的候选者。

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