Journal of Drug Delivery Science and Technology最新文献_第6页

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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引用次数: 0

Dual-ligand nanoprobes for fluorescence and magnetic particle imaging-guided glioma surgical resection 双配体纳米探针用于荧光和磁颗粒成像引导的胶质瘤手术切除

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.2025.107911

Yingzheng Zhao , Ailing Lu , Wen Wang , Hengcai Wang , Wenli Gao , Lei Chen , Xiaoyun Guan , Deli Zhuge , Bin Chen

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, with surgical resection remaining the mainstay of clinical treatment. However, its highly infiltrative growth pattern and indistinct tumor boundaries present significant challenges for complete surgical removal. In this study, we developed a dual-ligand modified nanoprobe (TR@SIL) co-functionalized with cyclic RGD peptide and transferrin (TF) to enhance GBM-targeting efficiency synergistically. To improve nanoprobe delivery across the brain-blood barrier (BBB), ultrasound-targeted microbubble destruction (UTMD) was employed as a noninvasive strategy to transiently open the BBB. TR@SIL co-encapsulates near-infrared dye IR780 and superparamagnetic iron oxide nanoparticles (SPIONs), enabling dual-modal fluorescence and magnetic particle imaging (MPI) of GBM. In vitro studies demonstrated significantly enhanced uptake of TR@SIL by GL261 glioma cells. In vivo imaging further confirmed that TR@SIL substantially increased both fluorescence and MPI signals at tumor sites. Under dual-modal imaging guidance, gliomas were accurately resected, leading to prolonged survival in glioma-bearing mice. In conclusion, we successfully developed a BBB-penetrating, glioma-targeting dual-modal imaging agent, providing a promising strategy for diagnosis, precise intraoperative navigation, and improved surgical outcomes in glioma therapy.

多形性胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤，手术切除仍然是临床治疗的主要方法。然而，其高度浸润性的生长模式和模糊的肿瘤边界对完全手术切除提出了重大挑战。在这项研究中，我们开发了一种双配体修饰的纳米探针（TR@SIL），与环RGD肽和转铁蛋白（TF）共功能化，协同提高gbm靶向效率。为了改善纳米探针通过脑血屏障（BBB）的传递，超声靶向微泡破坏（UTMD）被用作一种非侵入性策略来短暂打开脑血屏障。TR@SIL共封装近红外染料IR780和超顺磁性氧化铁纳米颗粒（SPIONs），实现GBM的双峰荧光和磁颗粒成像（MPI）。体外研究表明，GL261胶质瘤细胞对TR@SIL的摄取显著增强。体内成像进一步证实TR@SIL显著增加了肿瘤部位的荧光和MPI信号。在双模成像引导下，胶质瘤被准确切除，延长了胶质瘤小鼠的生存期。总之，我们成功开发了一种穿透血脑屏障、靶向胶质瘤的双模式显像剂，为胶质瘤治疗提供了一种有前途的诊断策略、精确的术中导航和改善的手术效果。

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引用次数: 0

Amalgamation of postbiotic, polysaccharide and plant flavonoid in nanostructured lipid carrier for treatment of rotenone-induced Parkinson's disease 生物后、多糖和植物类黄酮在纳米结构脂质载体中的融合治疗鱼藤酮诱导的帕金森病

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.2025.107930

Bushra Bashir , Monica Gulati , Sukriti Vishwas , Pooja Temgire , Puneet Kumar , Kaustubh Ajit Kolekar , Anuradha Acharya , Gaurav Gupta , Harish Dureja , Kamal Dua , Sachin Kumar Singh

A novel, multifunctional nanostructured lipid carrier (NLC) formulation has been developed by amalgamating a plant flavonoid, Xanthohumol (XHM), with postbiotic sodium butyrate (SB), and natural polysaccharides guar gum (GG) and pectin (PEC) to deliver multiple benefits of controlled release, gut microbiota modulation and neuroprotection. The optimized liquid NLC (L-XHM-NLC) was developed using Box-Behnken Design, followed by its solidification into solid NLC (SXHM-NLC) using SB and polysaccharides as both stabilizers and nutraceuticals. The final formulation demonstrated particle size of 112.0 nm, zeta potential of −10.6 mV, and entrapment efficiency EE of 98.7 %. In vitro release studies revealed 2.66-fold and 1.48-fold enhancement in the release of XHM from S-XHM-NLC as compared to naïve XHM and L-XHM-NLCs. The significant (P < 0.05) enhancement in Cmax and AUC was observed in the case of both S-XHM-NLC, with SB and without SB, indicating enhancement in absorption and oral bioavailability of XHM from NLCs as compared to naïve XHM. S-XHM-NLC with SB exhibited a 5.3-fold enhancement in AUC and a 4.7-fold enhancement in Cmax when compared to naïve XHM. Pharmacodynamic evaluations in the rotenone-induced PD model in rats showed that S-XHM-NLC with SB significantly improved motor coordination, grip strength, and sensory-motor function. Biochemical analyses revealed a 3.2-fold increase in dopamine levels, along with the marked elevation in antioxidant enzymes and reduction in oxidative stress markers. ELISA and Western blot analyses confirmed downregulation of pro-inflammatory cytokines and upregulation of tyrosine hydroxylase enzyme activity. Histopathological assessment corroborated the neuroprotective potential of the formulation by showing preserved neuronal integrity in the substantia nigra.

一种新型的、多功能的纳米结构脂质载体（NLC）配方由植物类黄酮、黄腐酚（XHM）、生物后丁酸钠（SB）、天然瓜尔胶（GG）和果胶（PEC）混合而成，具有控释、调节肠道微生物群和神经保护等多种益处。采用Box-Behnken设计方法制备最佳液体NLC (L-XHM-NLC)，并以SB和多糖作为稳定剂和营养制剂，将其固化为固体NLC （SXHM-NLC）。最终配方的粒径为112.0 nm， zeta电位为−10.6 mV，捕获效率为98.7%。体外释放研究显示，与naïve XHM和l -XHM- nlc相比，S-XHM-NLC的XHM释放量增加了2.66倍和1.48倍。S-XHM-NLC的Cmax和AUC均显著（P < 0.05）提高，无论是否添加SB，这表明与naïve XHM相比，nlc对XHM的吸收和口服生物利用度都有所提高。与naïve XHM相比，含SB的S-XHM-NLC的AUC增强了5.3倍，Cmax增强了4.7倍。鱼藤酮诱导PD大鼠模型的药效学评价显示，S-XHM-NLC加SB可显著改善运动协调性、握力和感觉运动功能。生化分析显示，多巴胺水平增加了3.2倍，同时抗氧化酶显著升高，氧化应激标志物显著减少。ELISA和Western blot分析证实，促炎细胞因子下调，酪氨酸羟化酶活性上调。组织病理学评估证实了该配方的神经保护潜力，显示在黑质中保留了神经元的完整性。

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引用次数: 0

Bis-MPA polymer inclusion complex/thiophene-acridine derivative: Antiparasitic and immunomodulatory potential against Leishmania infantum, Leishmania amazonensis and Schistosoma mansoni 双mpa聚合物包合物/噻吩-吖啶衍生物：对婴儿利什曼原虫、亚马逊利什曼原虫和曼氏血吸虫的抗寄生和免疫调节潜力

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.2025.107927

Diego Santa Clara Marques , Andreza Ribeiro Tavares , Lisandra da Silva Lima , Karla Crystina Costa dos Santos , Fábio André Brayner , Luiz Carlos Alves , Ricardo Olímpio de Moura , Ricardo Oliveira da Silva , Iane Bezerra Vasconcelos Alves , Severino Alves Junior , Iranildo José da Cruz Filho , Maria do Carmo Alves de Lima

Neglected tropical diseases (NTDs) remain a major global health challenge, particularly leishmaniasis and schistosomiasis. The scarcity of new therapeutic agents is partly attributed to the poor solubility of bioactive molecules. This study reports the development of an inclusion complex between the acridine–thiophene derivative 6ESTAC01 and the bis-MAP polymer (bis-MAP/6ESTAC01), aiming to enhance solubility and antiparasitic efficacy. The complex exhibited a 9.9-fold increase in solubility and significantly improved leishmanicidal and schistosomicidal activities. Against Leishmania infantum, IC₅₀ values for 6ESTAC01 were 11.32 ± 1.1 μM (promastigote) and 19.7 ± 2.1 μM (amastigote), whereas the complex displayed 5.48 ± 0.2 μM and 9.32 ± 0.5 μM, respectively. For L. amazonensis, activity increased 1.8-fold. In Schistosoma mansoni, the complex induced 89.2 % and 55.8 % mortality at 50 and 25 μM, surpassing the free compound. Moreover, bis-MAP/6ESTAC01 modulated Th1 immune responses, supporting intracellular parasite clearance. Interaction studies revealed moderate binding affinity to human serum albumin (K_sv = 3.77 × 10⁵ M⁻¹) and weak-to-moderate DNA interactions (K_sv = 6.26 × 10⁴ M⁻¹ for DAPI and 7.9 × 10³ M⁻¹ for acridine orange). These findings demonstrate that complexation with bis-MAP enhances 6ESTAC01 bioavailability and biological activity through improved solubility.

被忽视的热带病（NTDs）仍然是一个重大的全球卫生挑战，特别是利什曼病和血吸虫病。新治疗剂的缺乏部分归因于生物活性分子的溶解度差。本研究报道了吖啶-噻吩衍生物6ESTAC01与双- map聚合物（bis-MAP/6ESTAC01）之间的包合物，旨在提高其溶解度和抗寄生虫效果。该配合物的溶解度提高了9.9倍，并显著提高了杀利什曼原虫和杀血吸虫的活性。6ESTAC01对幼利什曼原虫的IC50值分别为11.32±1.1 μM （promastigote）和19.7±2.1 μM (amastigote)，而复合物对幼利什曼原虫的IC50值分别为5.48±0.2 μM和9.32±0.5 μM。amazon L.的活性增加了1.8倍。在曼氏血吸虫中，该复合物在50 μM和25 μM下的死亡率分别为89.2%和55.8%，高于游离复合物。此外，bis-MAP/6ESTAC01调节Th1免疫应答，支持细胞内寄生虫清除。相互作用研究显示，与人血清白蛋白的结合亲和力中等（Ksv = 3.77 × 105 M−1），DNA相互作用弱至中等（DAPI的Ksv = 6.26 × 104 M−1，吖啶橙的Ksv = 7.9 × 103 M−1）。这些结果表明，与bis-MAP络合可以通过改善溶解度来提高6ESTAC01的生物利用度和生物活性。

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引用次数: 0

Liver targeted nanomedicine for treatment of fibrosis and hepatocellular carcinoma: Emerging strategies in ligand-guided, stimuli-responsive and gene-based delivery 肝靶向纳米药物治疗纤维化和肝细胞癌：配体引导、刺激反应和基于基因的递送的新策略

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.2025.107935

Poonam Sahu, Trilochan Satapathy

Liver diseases, including hepatic fibrosis, non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC), remain major global health burdens due to their silent progression and limited therapeutic efficacy. Advances in liver-targeted nanomedicine have enhanced treatment precision and minimized systemic toxicity. Literature from last 10 years highlights lipid-based, polymeric, inorganic, and hybrid nanocarriers functionalized with ligands such as N-Acetylgalactosamine(GalNAc), hyaluronic acid (HA), and peptide aptamers for specific hepatic targeting. Stimuli-responsive platforms triggered by pH, redox, or enzymatic cues enable localized and controlled drug release within diseased tissues. Non-viral systems delivering small interfering RNA (siRNA), Messenger RNA (mRNA), and Clustered Regularly Interspaced Short Palindromic Repeats- Cas9 (CRISPR-Cas9) components achieve effective gene modulation with reduced off-target effects. Biomimetic and polysaccharide-based self-assembling nanocarriers further improve biocompatibility and immune evasion. AI-driven in-Silico modeling supports nanocarrier optimization and predictive performance. Overall, the integration of nanocarrier engineering, ligand-directed targeting, and gene-editing technologies is revolutionizing liver disease therapy. Despite progress, challenges in bio-safety, scalability, and clinical translation persist. The authors put their effort to emphasizethe need for interdisciplinary strategies and personalized nanomedicine approaches to achieve safe, efficient, and clinically translatable liver therapeutics.

肝脏疾病，包括肝纤维化、非酒精性脂肪性肝炎（NASH）和肝细胞癌（HCC），由于其悄无声息的进展和有限的治疗效果，仍然是全球主要的健康负担。肝脏靶向纳米药物的进展提高了治疗精度，降低了全身毒性。过去10年的文献强调了基于脂质、聚合物、无机和杂化的纳米载体与配体的功能化，如n -乙酰半乳糖胺（GalNAc）、透明质酸（HA）和用于特定肝脏靶向的肽适体。由pH值、氧化还原或酶线索触发的刺激响应平台能够在病变组织中局部和受控的药物释放。递送小干扰RNA （siRNA）、信使RNA （mRNA）和聚集规则间隔短回文重复序列Cas9 （CRISPR-Cas9）组件的非病毒系统实现了有效的基因调控，减少了脱靶效应。仿生和基于多糖的自组装纳米载体进一步提高了生物相容性和免疫逃避。人工智能驱动的硅建模支持纳米载体优化和预测性能。总的来说，纳米载体工程、配体定向靶向和基因编辑技术的整合正在彻底改变肝病治疗。尽管取得了进展，但生物安全、可扩展性和临床转化方面的挑战仍然存在。作者努力强调跨学科策略和个性化纳米医学方法的必要性，以实现安全、有效和临床可翻译的肝脏治疗。

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引用次数: 0

Caffeic acid–functionalized silver nanoparticles for skin therapy: Antioxidant, antibacterial, and anti-melanogenic properties 咖啡酸功能化纳米银用于皮肤治疗：抗氧化、抗菌和抗黑素生成特性

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.2025.107937

Siham Bouaouz , Rebeca Lozano , Francisca I. Bravo , Begoña Muguerza , Miquel Mulero , Enrique Calvo , Paula Ortega , F. Javier de la Mata

Multifunctional nanomaterials offers promising strategies for the treatment of skin disorders involving oxidative stress, microbial infections, and hyperpigmentation. Herein, we report the covalent functionalization of silver nanoparticles AgNP-(S-PEG2K-CA) (AgNP-1) with caffeic acid, a natural polyphenol with well-known antioxidant and anti-melanogenic properties. Additionally, a cationic carbosilane wedge was introduced to confer antibacterial functionality, resulting in a heterofunctional nanoconjugate, AgNP-(S-PEG2K-CA)(S-G₁-NMe₃Cl) (AgNP-2), with enhanced biological performance. The physicochemical characterization confirmed successful functionalization and stability of the nanoparticles. Biological assays showed that the silver nanoparticles exhibited antioxidant activity (AgNP-1: IC₅₀ = 4.18 μg/mL, EC₅₀ = 0.57 μg/mL; AgNP-2: IC₅₀ = 12.35 μg/mL, EC₅₀ = 0.87 μg/mL), which was attributed to the presence of caffeic acid on their surface and AgNP-2 exhibited strong antibacterial effects, particularly against Staphylococcus aureus (MIC 4 mgL⁻¹ and MBC 8 mgL⁻¹) and Escherichia coli (MIC 4 mgL⁻¹ and MBC 8 mgL⁻¹). In vitro experiments using a mammalian melanocyte model (B16F10 cells) revealed for both nanoparticles significantly inhibited melanin synthesis at 20 μg/mL reduced the accumulation of intracellular melanin in a similar extent as kojic acid at 1000 μg/mL. Finally, permeation studies using Franz diffusion cells, combined with UV–Vis spectroscopy and ICP-OES analysis to detect nanoparticle concentration, showed that neither AgNP-1 nor AgNP-2 were able to cross the membrane, indicating that they remain confined to the membrane surface. This localization is crucial for minimizing the risk of systemic exposure, thereby supporting the safety and suitability of these nanoparticles for topical applications.

多功能纳米材料为治疗包括氧化应激、微生物感染和色素沉着在内的皮肤疾病提供了有前途的策略。本文中，我们报道了银纳米粒子AgNP-(S-PEG2K-CA) （AgNP-1）与咖啡酸（一种众所周知具有抗氧化和抗黑色素生成特性的天然多酚）的共价功能化。此外，引入阳离子碳硅烷楔形物来赋予抗菌功能，从而产生异功能纳米偶联物AgNP-(S-PEG2K-CA)(S-G1-NMe3Cl) (AgNP-2)，具有增强的生物性能。物理化学表征证实了纳米颗粒的成功功能化和稳定性。生物实验表明，银纳米颗粒具有抗氧化活性（AgNP-1: IC50 = 4.18 μg/mL, EC50 = 0.57 μg/mL; AgNP-2: IC50 = 12.35 μg/mL, EC50 = 0.87 μg/mL），这是由于其表面存在咖啡酸，AgNP-2具有较强的抗菌作用，特别是对金黄色葡萄球菌（MIC 4 mgL−1和MBC 8 mgL−1）和大肠杆菌（MIC 4 mgL−1和MBC 8 mgL−1）。在哺乳动物黑素细胞模型（B16F10细胞）的体外实验中发现，这两种纳米颗粒在20 μg/mL浓度下显著抑制黑色素合成，其减少细胞内黑色素积累的程度与1000 μg/mL浓度的曲酸相似。最后，使用Franz扩散池进行渗透研究，结合UV-Vis光谱和ICP-OES分析检测纳米颗粒浓度，发现AgNP-1和AgNP-2都不能穿过膜，表明它们仍然被限制在膜表面。这种定位对于最小化全身暴露的风险至关重要，从而支持这些纳米颗粒局部应用的安全性和适用性。

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引用次数: 0

Unification and characterization of polyvinyl pyrrolidone -dextran sulfate sodium, and cefixime nanofibers for antibacterial potency 聚乙烯吡咯烷酮-葡聚糖硫酸钠与头孢克肟纳米纤维抗菌效能的统一与表征

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.2025.107931

Sanjivani S. Panditkar , Wasudeo B. Gurnule , Anita Shekhawat , D. Saravanan , Prajakta U. Waghe

The development of localized antibiotic delivery systems is essential for improving therapeutic efficiency and reducing systemic side effects associated with conventional dosing. Electrospun nanofibers offer high surface area, tunable porosity, and suitability for sustained drug release. In this study, cefixime-loaded polyvinylpyrrolidone (PVP)/Dextran Sulfate Sodium (DSS) nanofibers are fabricated via blend electrospinning to enhance antibacterial performance against clinically relevant pathogens. The optimized PVP–DSS formulation produced smooth, bead-free fibers with diameters of 250–350 nm, confirmed by SEM. FTIR analysis indicated hydrogen-bond–mediated interactions between the drug and polymers, while XRD demonstrated amorphous molecular dispersion of cefixime, supporting improved solubility and matrix stability. Thermogravimetric analysis (TGA) further revealed superior thermal resistance of the composite fibers compared to the individual components. Antibacterial activity evaluated using disc diffusion showed pronounced inhibition zones (12–25 mm) against Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus, confirming effective drug retention. These findings highlight the potential of PVP/DSS-based nanofibrous scaffolds as promising candidates for controlled antibiotic efficacy.

局部抗生素递送系统的发展对于提高治疗效率和减少与常规剂量相关的全身副作用至关重要。静电纺纳米纤维具有高表面积、可调孔隙率和持续药物释放的适用性。在这项研究中，通过共混静电纺丝制备了头孢昔肟负载的聚乙烯吡罗烷酮(PVP)/葡聚糖硫酸钠（DSS）纳米纤维，以增强对临床相关病原体的抗菌性能。经扫描电镜（SEM）证实，优化后的PVP-DSS配方可获得直径为250-350 nm的光滑无珠纤维。FTIR分析表明药物与聚合物之间存在氢键介导的相互作用，而XRD分析表明头孢克肟的分子分散呈无定形，支持提高溶解度和基质稳定性。热重分析（TGA）进一步揭示了复合纤维与单个组分相比具有优越的耐热性。用圆盘扩散法评估的抗菌活性显示，对大肠杆菌、肺炎克雷伯菌和金黄色葡萄球菌有明显的抑制区（12-25 mm），证实了有效的药物保留。这些发现突出了PVP/ dss纳米纤维支架作为控制抗生素疗效的有希望的候选者的潜力。

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引用次数: 0

Surfactin as a biosurfactant enhancing the adjuvant activity of an essential oil-based nanoemulsion in an experimental inactivated vaccine against enterotoxigenic Escherichia coli (ETEC) 作为生物表面活性剂的表面素增强了实验性产肠毒素大肠杆菌灭活疫苗中精油基纳米乳的佐剂活性

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.2025.107929

María de L. Vancolli , María E. Cecchini , Sofía Arsaute , Nahuel Matías Camacho , Ivana D. Montironi , Romina Bellingeri , María L. González Pereyra , Laura N. Cariddi

Nanoemulsions have shown excellent results as vaccine adjuvants. The stability of nanoemulsions can be improved by adding specific emulsifiers, generally chemical surfactant molecules. However, the search for natural substitutes for these surfactants is a booming topic. Previous study has demonstrated that nanoemulsions based in Minthostacchys verticillata essential oil (EO) using Tween® 80 and Span® 60 as surfactants have immunostimulatory properties when used as adjuvants in experimental vaccine. The aim of this study was to evaluate the ability of surfactin (Srf) as a biosurfactant to enhance the adjuvant effect of M. verticillata EO-based nanoemulsions (NE) in an experimental inactivated vaccine against enterotoxigenic Escherichia coli (ETEC). Four NE were formulated varying the proportions of EO, Srf, Tween and water. NE4 (20 % EO, 1 % Srf, 1 % Tween® 80, 68 % water) was the most stable, with a particle size of 143 nm and a polydispersity index (PDI) of 0.21. NE4 was non-toxic to Caco-2 cells at concentrations below 750 μg/mL. Scanning electron microscopy revealed an interconnected matrix of NE4 with inactivated ETEC. BALB/c mice were immunized with inactivated ETEC alone or combined with incomplete Freund's adjuvant (IFA) or NE4 at different concentrations. NE4-adjuvanted vaccine significantly increased IgG levels with opsonizing potential, comparable to IFA. These results suggest that Srf acts as an effective biosurfactant that enhances the adjuvant activity of M. verticillata EO. These results highlight the potential of N4 to serve as a novel adjuvant in next-generation vaccines aimed at controlling veterinary diseases.

纳米乳剂作为疫苗佐剂已显示出优异的效果。通过添加特定的乳化剂，通常是化学表面活性剂分子，可以提高纳米乳的稳定性。然而，寻找这些表面活性剂的天然替代品是一个蓬勃发展的话题。先前的研究表明，使用Tween®80和Span®60作为表面活性剂的基于Minthostacchys verticillata精油（EO）的纳米乳液作为实验性疫苗佐剂时具有免疫刺激特性。本研究的目的是评估表面活性剂表面素（Srf）在抗肠道产毒素大肠杆菌（ETEC）灭活疫苗中增强基于M. verticillata eo纳米乳（NE）佐剂作用的能力。以EO、Srf、Tween和water的不同比例配制了4种NE。NE4 （20% EO, 1% Srf, 1% Tween®80,68%水）最稳定，粒径为143 nm，多分散指数（PDI）为0.21。在浓度低于750 μg/mL时，NE4对Caco-2细胞无毒性。扫描电镜显示NE4与失活ETEC相互连接的基质。分别用灭活ETEC单独或与不完全弗氏佐剂（IFA）或不同浓度的NE4联合免疫BALB/c小鼠。ne4佐剂疫苗显著提高了具有活化潜能的IgG水平，与IFA相当。这些结果表明Srf是一种有效的生物表面活性剂，可以增强乳突菌的佐剂活性。这些结果突出了N4作为一种新型佐剂用于控制兽医疾病的下一代疫苗的潜力。

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引用次数: 0

Mannose-functionalized Nano-Therapeutics: A targeted strategy for combating bacterial infections 甘露糖功能化纳米疗法：对抗细菌感染的靶向策略

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-15 DOI: 10.1016/j.jddst.2025.107924

Devika Sajeev , Padmaja A. Shenoy , Usha Y. Nayak

Bacterial infections continue to pose a severe global health risk, which is compounded by the emergence of multidrug-resistant strains and the protective nature of biofilms. Conventional antibiotic therapies are frequently proven ineffective because of the challenges associated with bacterial invasion mechanisms and drug delivery mechanisms. Mannose-functionalized therapies have emerged as promising strategies for targeted drug delivery, emphasizing the interaction between mannose moieties and particular receptors or bacterial adhesins. Mannosylation increases drug targeting and accumulation at the site of infection, which enhances biofilm penetration and promotes macrophage-targeted drug administration via receptor-mediated endocytosis. This review examines both natural and synthetic mannosylation methods in nanocarriers, focusing on design, including chemical conjugation and enzymatic glycosylation, while detailing current progress and applications in nanodrug delivery systems, including liposomes, nanoparticles, micelles, and hydrogels, in antibacterial therapies. Mannose-modified systems demonstrate enhanced effectiveness in combating infections induced by pathogens such as E. coli, Klebsiella pneumoniae, and Mycobacterium tuberculosis. The strong binding affinity of mannose derivatives to bacterial adhesins, particularly Fim H, is further supported by in silico studies. The use of mannosylated drug carriers reduces systemic toxicity and antibiotic resistance while increasing therapeutic efficacy. Despite promising preclinical findings and ongoing patent developments, issues with stability, scalability, and regulatory procedures still exist. However, mannosylation offers a promising carbohydrate-based approach to targeted antibacterial therapy, particularly in the fight against bacterial infections that are resistant to multiple drugs.

细菌感染继续构成严重的全球健康风险，而耐多药菌株的出现和生物膜的保护性使这种风险更加严重。由于与细菌侵袭机制和药物传递机制相关的挑战，常规抗生素治疗经常被证明无效。甘露糖功能化疗法已成为有希望的靶向药物递送策略，强调甘露糖部分与特定受体或细菌粘附素之间的相互作用。甘露糖基化增加了药物在感染部位的靶向和积累，从而增强了生物膜的渗透，并通过受体介导的内吞作用促进了巨噬细胞靶向药物的给药。本文综述了纳米载体中的天然和合成甘露糖基化方法，重点是设计，包括化学偶联和酶糖基化，同时详细介绍了纳米药物传递系统的最新进展和应用，包括脂质体、纳米颗粒、胶束和水凝胶，以及抗菌治疗。甘露糖修饰的系统在对抗由大肠杆菌、肺炎克雷伯菌和结核分枝杆菌等病原体引起的感染方面显示出更高的有效性。甘露糖衍生物对细菌黏附素的强结合亲和力，特别是H膜，进一步得到了硅研究的支持。甘露糖基化药物载体的使用降低了全身毒性和抗生素耐药性，同时提高了治疗效果。尽管有临床前研究结果和正在进行的专利开发，但稳定性、可扩展性和监管程序方面的问题仍然存在。然而，甘露糖基化为靶向抗菌治疗提供了一种很有前途的基于碳水化合物的方法，特别是在对抗多种药物耐药的细菌感染方面。

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引用次数: 0