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Dual mechanistic approach utilizing pH- and time- responsive bromelain laden polymeric nanoparticles for colon cancer management 双重机制的方法利用pH和时间响应菠萝蛋白酶负载聚合物纳米颗粒结肠癌的管理
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-26 DOI: 10.1016/j.onano.2025.100272
Manu Sharma, Namita Badoniya
Emerging evidences confirming bromelain’s potential to induce apoptosis and inhibit tumor progression highlights its prospective as adjunctive therapeutic in colorectal cancer malignancies. Despite, high oral doses coupled with poor bioavailability remarkably limits bromelain’s clinical utility, underscoring the necessity of use of innovative delivery strategies. Therefore, the current invention was designed to develop dual pH- and time-responsive bromelain-loaded nanoformulation (Br-PNPs) for controlled and precise delivery to colon with high drug loading capacity and enhanced therapeutic efficacy. pH responsive spherical shaped mucoadhesive nanosized (89.02±6.23 nm) Br-PNPs underscores their potential of minimizing gastric exposure while swelling and mucoadhesivity assured sustained release in colon. Lower IC50 (16.25µg/ml) along with enhanced colon drug concentration attained by Br-PNPs assured their effective colon targeting potential. Br-PNPs significantly reduced disease activity index, tumor burden, aberrant crypt foci and hyperplastic lesions in colon alongside oxidative stress and immunological biomarkers in chemically induced colon cancer model (DMH+DSS) in Wistar rat. The preclinical findings suggested that Br-PNPs have opened up new horizons for establishment of promising contender for colon cancer management in near future.
新出现的证据证实菠萝蛋白酶具有诱导细胞凋亡和抑制肿瘤进展的潜力,这突出了其作为结直肠癌恶性肿瘤辅助治疗的前景。尽管如此,高口服剂量加上较差的生物利用度显著限制了菠萝蛋白酶的临床应用,强调了使用创新给药策略的必要性。因此,本发明旨在开发双重pH和时间响应的菠萝蛋白酶负载纳米制剂(Br-PNPs),以控制和精确地递送到结肠,具有高载药能力和增强的治疗效果。pH响应球形黏附纳米Br-PNPs(89.02±6.23 nm)强调了它们在减少胃暴露的同时肿胀和黏附确保在结肠中持续释放的潜力。Br-PNPs具有较低的IC50(16.25µg/ml)和较高的结肠药物浓度,确保了其有效的结肠靶向潜力。在化学诱导结肠癌模型(DMH+DSS)中,Br-PNPs显著降低Wistar大鼠的疾病活动指数、肿瘤负担、异常隐窝灶和结肠增殖性病变,以及氧化应激和免疫生物标志物。临床前研究结果表明,Br-PNPs为在不久的将来建立有希望的结肠癌治疗竞争者开辟了新的视野。
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引用次数: 0
Green-synthesized selenium nanoparticles overcoming methotrexate resistance in colorectal cancer 绿色合成纳米硒克服了结直肠癌对甲氨蝶呤的耐药性
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-22 DOI: 10.1016/j.onano.2025.100269
Mohammed S. Saddik , Basima A.A. Saleem , Ali Khames , Ahmed Adel Alaa-Eldin , Mohamed Ahmed , Hesham.A. Eliwa , Mostafa F. Al-Hakkani , Ahmed M. Ashour , Hamada Hashem , Mohamad A. Ismail , Amany A. Abdel-Rheem

Objective

Colorectal cancer (CRC) therapy with methotrexate (MTX) is limited by toxicity and resistance. This study developed eco-friendly selenium nanoparticles (SeNPs) to enhance MTX delivery and overcome resistance.

Methods

SeNPs were synthesized using a green reduction method and optimized via a Box–Behnken design. Characterization confirmed spherical nanoparticles with an average size of 20–30 nm. MTX loading efficiency (LE%) and release behavior were measured, and biological evaluation was conducted in HCT116 colorectal cancer cells through cytotoxicity, apoptosis (Annexin V/7-AAD), and efflux-transporter assays.

Results

Optimized SeNPs achieved an MTX loading efficiency of ≈48–52 %, with controlled early-phase release. MTX–SeNPs markedly enhanced cytotoxicity, reducing the IC₅₀ to 62.4 µg/mL, compared with 186.6 µg/mL for MTX alone—representing a ∼67 % reduction in required dose. Docking analysis showed selenium interacting with human glutathione reductase, supporting the observed increase in ROS and apoptosis.

Conclusions

Green-synthesized SeNPs significantly improve MTX efficacy by enhancing drug retention, suppressing efflux activity, and reducing resistance. These findings highlight MTX–SeNPs as a promising strategy for CRC treatment and justify further in vivo investigation.
目的甲氨蝶呤(MTX)治疗结直肠癌(CRC)存在一定的毒副作用和耐药性。本研究开发了生态友好的硒纳米颗粒(SeNPs)来增强MTX的递送和克服耐药性。方法采用绿色还原法合成senps,并采用Box-Behnken设计优化。表征证实了平均尺寸为20-30 nm的球形纳米颗粒。测定MTX的加载效率(LE%)和释放行为,并通过细胞毒性、凋亡(Annexin V/7-AAD)和外排转运体测定对HCT116结直肠癌细胞进行生物学评价。结果优化后的SeNPs的MTX加载效率为≈48 ~ 52%,早期释放可控。MTX - senps显着增强了细胞毒性,将IC₅0降低到62.4µg/mL,而单独使用MTX的IC₅0为186.6µg/mL,这意味着所需剂量减少了67%。对接分析显示,硒与人谷胱甘肽还原酶相互作用,支持观察到的ROS和细胞凋亡的增加。结论格林合成的SeNPs通过增强药物潴留、抑制外排活性、降低耐药,显著提高MTX的疗效。这些发现突出了MTX-SeNPs作为一种有前景的CRC治疗策略,并证明了进一步的体内研究的合理性。
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引用次数: 0
An overview of the alarming impediments encountered while establishing an apposite IVIVC of nanomedicines necessitated its regulatory approval 概述了在建立纳米药物的适当IVIVC时遇到的令人震惊的障碍,有必要批准其监管部门
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-22 DOI: 10.1016/j.onano.2025.100271
Nandakumar Selvasudha , Joseph Pushpa Sweety , Gover Antoniraj M , Kandasamy Ruckmani
<div><div>For the past three decades, the principle of nanotechnology has been widely employed to develop pharmaceuticals and bio-pharmaceuticals that are successful for many disease therapies. Several commercially available approved nanomedicines are more efficacious than conventional dosage forms and successfully manage many diseases. The patient's well-being and the certainty to resolve the unresolved challenges of medical science became realistic due to the advent of novel pharmaceutical products based on nanotechnology. These benefits are observed as in humans, the absorption profile of a drug fabricated into nanoparticles varies widely with that of its conventional dosage forms mainly due to the physicochemical modifications and results in highly deviating in-vitro and in-vivo data for the same drug when administered as nanoparticles. The researchers and regulators must frame new guidelines that guide the pharmaceutical industry to develop novel nanomedicines that conform to the desired safety and efficacy. The nanoparticles translational research conducted at the academic level is mainly developing, and the scale-up techniques of the clinically approved nanomedicines are yet to be optimized from the perspective of the manufacturer as well as the regulatory authorities. The IVIVC serves as a reference document that reinforces the pharmaceutical industries to substantiate and expedite the credentials of an oral dosage form about the New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or Antibiotic Drug Application (AADA). A poor in-vitro in-vivo correlation (IVIVC) marks a constraint factor, which declines the clinical approval for nanomedicine and its commerce. As on date, neither any specific regulatory guidelines nor any specific calculation methods have been drafted that facilitate the determination of the IVIVC for nanomedicine. Most of the research scientists involved in developing nano/micro/macro formulations do not consider IVIVC an essential criterion. Therefore, a lag in assessing the formulation of assured quality for the next phase happens in the drug development cycle, which terminates the formulation mostly at its pilot scale rather than for its succession as a viable market product. In the pharmaceutical industries, the necessity for IVIVC has been expanded to a greater extent, and a strong IVIVC is recommended to approve the developed nanoformulations of poorly soluble drugs; thus, an appropriate IVIVC model shall be established to expedite the regulatory process for easy and rapid market approval of the developed nanomedicine.</div><div>The objective of the present review includes examining and considering the various associated factors involved in the development of an IVIVC model for nanomedicine, viz., Physico-chemical characteristics and bio-pharmaceutical factors (Formulation and physiological factors); to deliberate on the pros and cons of the various in-vitro dissolution study methods with due consid
在过去的三十年里,纳米技术的原理被广泛应用于开发药物和生物药物,这些药物和生物药物成功地治疗了许多疾病。几种市售的经批准的纳米药物比传统剂型更有效,并成功地治疗了许多疾病。由于基于纳米技术的新型医药产品的出现,病人的健康和解决医学未解决挑战的确定性变得现实。在人体中观察到这些益处,制成纳米颗粒的药物的吸收谱与其常规剂型的吸收谱差异很大,主要是由于物理化学修饰,并且当以纳米颗粒给药时,同一药物的体外和体内数据存在高度偏差。科学家和管理者必须制定新的指导方针,指导制药业开发符合预期安全性和有效性的新型纳米药物。学术层面的纳米颗粒转化研究主要处于发展阶段,临床批准的纳米药物的放大技术从生产企业和监管部门的角度来看都有待优化。IVIVC作为一份参考文件,加强制药行业证实和加快口服剂型关于新药申请(NDA)、简略新药申请(ANDA)或抗生素药物申请(AADA)的凭证。较差的体外体内相关性(IVIVC)是制约纳米药物临床批准和商业化的一个制约因素。迄今为止,还没有起草任何具体的监管指南或任何具体的计算方法来促进纳米药物IVIVC的确定。大多数参与开发纳米/微/宏观配方的研究科学家并不认为IVIVC是一个必要的标准。因此,在药物开发周期中,评估下一阶段质量有保证的配方会出现滞后,这主要是在其中试规模时终止配方,而不是在其作为可行市场产品的继承时终止配方。在制药行业,IVIVC的必要性已经扩大到更大的程度,并且建议使用强大的IVIVC来批准开发的难溶性药物的纳米配方;因此,应该建立一个合适的IVIVC模型,以加快监管过程,使所开发的纳米药物容易和快速地获得市场批准。本综述的目的包括审查和考虑纳米医学IVIVC模型开发中涉及的各种相关因素,即物理化学特性和生物制药因素(配方和生理因素);综合考虑各种体外溶出度研究方法的优缺点,并考虑受试者之间的差异,采用合适的方法准确预测体内吸收,以获得良好的IVIVC。这篇综述突出强调了与纳米药物监管批准相关的关键因素,并进一步探讨了遵守当前国际监管指南的各种研究工作。
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引用次数: 0
Formulation and characterization of dolutegravir sodium-loaded nanostructured lipid carrier in situ gel for targeted brain delivery via intranasal route dolute重力韦钠负载纳米结构脂质载体原位凝胶的制备和表征
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-20 DOI: 10.1016/j.onano.2025.100270
Salam Shanta Taher, Khalid K. Al-Kinani
Effective delivery of antiretroviral drugs to the brain is a major hurdle in treating central nervous system (CNS) HIV infections. This study developed an intranasal in situ gel containing dolutegravir sodium-loaded nanostructured lipid carriers (DTGs-NLCs) for targeted nose-to-brain delivery. DTGs-NLCs were prepared using a modified melt emulsification-ultrasonication method, yielding nanocarriers with a size of 80.8 ± 10.4 nm, zeta potential of –13±1.4 mV, and entrapment efficiency of 80.7 ± 0.48 %. These NLCs were incorporated into a thermosensitive in situ gel matrix composed of poloxamer 407 and carbopol 934P. The in vitro drug release from the gel was significantly enhanced compared to the free drug (p < 0.05). Rheological studies confirmed the formulation’s non-Newtonian behavior, good spreadability (5.9 ± 0.13 cm), and strong mucoadhesiveness (1116.86 ± 20 dyne/cm²). Safety evaluations demonstrated excellent hemocompatibility and biocompatibility. Pharmacokinetic studies revealed that intranasal administration achieved higher brain concentrations (Cmax: 35.4 ± 3.6 µg/g; AUC₀–₄₈: 193.22±14.66 µg·h/g) and faster absorption (Tmax: 1 h) than intravenous delivery. These results indicate that the DTGs-NLC in situ gel offers a safe, non-invasive, and efficient approach for enhanced brain targeting, showing great promise for treating CNS complications of HIV, including neuroAIDS.
有效地将抗逆转录病毒药物输送到大脑是治疗中枢神经系统(CNS) HIV感染的主要障碍。本研究开发了一种含多替重力韦钠负载纳米结构脂质载体(DTGs-NLCs)的鼻内原位凝胶,用于靶向鼻至脑递送。采用改进的熔融乳化-超声法制备了DTGs-NLCs,得到的纳米载体尺寸为80.8±10.4 nm, zeta电位为-13±1.4 mV,包封效率为80.7±0.48%。这些NLCs被掺入由poloxam407和carbopol 934P组成的热敏原位凝胶基质中。与游离药物相比,凝胶的体外药物释放明显增强(p < 0.05)。流变学研究证实了该配方具有非牛顿力学性质,良好的涂覆性(5.9±0.13 cm)和较强的黏附性(1116.86±20达因/cm²)。安全性评价显示其具有良好的血液相容性和生物相容性。药代动力学研究表明,与静脉给药相比,鼻内给药具有更高的脑浓度(Cmax: 35.4±3.6µg/g; AUC₀-₄₈:193.22±14.66µg·h/g)和更快的吸收(Tmax: 1 h)。这些结果表明,DTGs-NLC原位凝胶为增强脑靶向提供了一种安全、无创、有效的方法,在治疗包括神经艾滋病在内的HIV中枢神经系统并发症方面显示出巨大的希望。
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引用次数: 0
Response surface methodology - optimized niosomes encapsulating whole tomato extract: Release profile and mechanistic insights for UVB protection and anti-melanogenesis applications 响应面方法-优化的包封整个番茄提取物的囊体:释放剖面和对UVB保护和抗黑素生成应用的机制见解
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-20 DOI: 10.1016/j.onano.2025.100267
Nattawadee Kanpipit , Sakornchon Mattariganont , Likit Temprom , Prutchayawoot Thopan , Khomsorn Lomthaisong , Sriprajak Krongsuk , Suthasinee Thapphasaraphong
This study presents the development and characterization of a novel niosome delivery system incorporating whole tomato extract for topical application. The formulation was optimized using a Box–Behnken design (BBD) by response surface methodology (RSM) to achieve high entrapment efficiency, small vesicle size, and low polydispersity index (PDI). The optimal formulation (2 mM Span 60, 1 mM cholesterol, 1 % extract) yielded an entrapment efficiency of 90.34 %, particle size of 222.06 nm, and PDI of 0.34. Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) analyses confirmed successful encapsulation and nanoscale spherical morphology. In vitro release studies demonstrated distinct kinetic behaviors: the whole extract followed Higuchi model, while lycopene exhibited zero-order model. The optimized tomato extract–loaded niosomes (TNS) exhibited enhanced stability and demonstrated significant biological activity, including ultraviolet ̶ B (UVB) protection in immortalized human keratinocyte cell lines (HaCaT) and anti-melanogenic effects in murine melanoma cell lines (B16F10). Notably, tomato extract–loaded niosomes (TNS) significantly downregulated the expression of melanogenesis-related proteins, microphthalmia-associated transcription factor (MITF) and tyrosinase, as confirmed by Western blot analysis. These findings support the potential use of tomato extract-loaded niosomes (TNS) as multifunctional cosmetic ingredients for photoprotection and skin whitening applications.
本研究提出了一种新的niosome输送系统的发展和特性,该系统包含全番茄提取物用于局部应用。采用响应面法(RSM)对该配方进行Box-Behnken设计(BBD)优化,以获得高捕获效率、小囊泡尺寸和低多分散性指数(PDI)。最佳配方(2 mM Span 60, 1 mM胆固醇,1%提取物)的包封效率为90.34%,粒径为222.06 nm, PDI为0.34。傅里叶变换红外光谱(FTIR)和透射电子显微镜(TEM)分析证实了成功的封装和纳米级球形形貌。体外释放研究显示了不同的动力学行为:整个提取物符合Higuchi模型,而番茄红素则符合零级模型。优化后的番茄提取物负载niosomes (TNS)表现出更高的稳定性和显著的生物活性,包括对永生化人角质形成细胞系(HaCaT)的紫外线B (UVB)保护和对小鼠黑色素瘤细胞系(B16F10)的抗黑素生成作用。值得注意的是,经Western blot分析证实,番茄提取物装载的niosomes (TNS)显著下调了黑色素生成相关蛋白、小眼相关转录因子(MITF)和酪氨酸酶的表达。这些发现支持了番茄提取物负载niosomes (TNS)作为光保护和皮肤美白的多功能化妆品成分的潜在用途。
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引用次数: 0
Nanodiagnostics and nanotoxicology: A systematic review and meta-analysis on nanoparticle applications and safety in metabolic organs 纳米诊断和纳米毒理学:纳米颗粒在代谢器官中的应用和安全性的系统综述和荟萃分析
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-19 DOI: 10.1016/j.onano.2025.100266
Sruti Murali , Jayamani Thomas , John Abraham , Vignesh Kanna , Sivaramakrishnan Ramachandiran , Suruthi SS

Background

Nanotechnology is reshaping the biomedical landscape by offering unprecedented capabilities in disease diagnostics, targeted therapy, and biosensing. Nanoparticles (NPs), owing to their unique physicochemical properties, enable ultra-sensitive biomarker detection, real-time monitoring, and minimally invasive assays across oncology, infectious diseases, and neurology. However, their biological interactions also raise significant concerns regarding organ-specific toxicity, particularly in metabolic systems.

Objective

This systematic review and meta-analysis aim to integrate current evidence on nanoparticle-based diagnostic applications with emerging insights into their toxicological impacts on key metabolic organs — liver, kidney, pancreas, spleen, and adipose tissue. It further examines mechanistic pathways, dose-dependent effects, and translational challenges to bridge the gap between innovation and biosafety.

Methods

A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar from January 2015 to October 2025 following PRISMA 2020 guidelines. Eligible studies reported quantitative diagnostic performance metrics (e.g., limit of detection, sensitivity, multiplexing capacity) or biological outcomes (e.g., oxidative stress, apoptosis, fibrosis, endocrine disruption) related to NP exposure. Meta-analytic synthesis was performed on 42 studies reporting comparable quantitative toxicity data.

Results

Diagnostic applications of metallic, polymeric, photonic, and hybrid nanoparticles demonstrated up to a 1000-fold improvement in sensitivity over conventional assays, with mean detection limits reaching the femtomolar range. However, pooled toxicity analysis revealed significant organ-specific risks: hepatic ROS generation (standardized mean difference [SMD] = 1.42, 95 % CI: 1.10–1.75), renal tubular apoptosis (SMD = 1.27, 95 % CI: 0.94–1.61), and β-cell impairment (SMD = 1.18, 95 % CI: 0.88–1.49). Translational challenges remain due to poor clearance kinetics, chronic inflammation, and incomplete regulatory frameworks.

Conclusion

Nanoparticles hold transformative potential in precision diagnostics, but their clinical adoption demands a nuanced understanding of toxicological trade-offs. Future research must focus on biodegradable and renal-clearable materials, mechanistically guided design strategies, standardized toxicological protocols, and AI-driven predictive models. This review provides a dual-perspective framework that integrates diagnostic breakthroughs with biosafety imperatives, guiding the next phase of nanomedicine toward safe and effective clinical translation.
纳米技术在疾病诊断、靶向治疗和生物传感方面提供了前所未有的能力,正在重塑生物医学领域。纳米粒子(NPs),由于其独特的物理化学性质,使超灵敏的生物标志物检测,实时监测和微创分析跨越肿瘤学,感染性疾病和神经病学。然而,它们的生物相互作用也引起了对器官特异性毒性的重大关注,特别是在代谢系统中。本系统综述和荟萃分析旨在整合纳米颗粒诊断应用的现有证据,以及纳米颗粒对关键代谢器官(肝、肾、胰腺、脾脏和脂肪组织)毒理学影响的新见解。它进一步研究了机制途径、剂量依赖效应和转化挑战,以弥合创新与生物安全之间的差距。方法按照PRISMA 2020指南,于2015年1月至2025年10月对PubMed、Scopus、Web of Science和谷歌Scholar进行综合文献检索。符合条件的研究报告了与NP暴露相关的定量诊断性能指标(如检测限、灵敏度、多路复用能力)或生物学结果(如氧化应激、细胞凋亡、纤维化、内分泌干扰)。对42项报告可比较定量毒性数据的研究进行荟萃分析综合。结果金属、聚合物、光子和混合纳米颗粒的诊断应用表明,与传统分析相比,灵敏度提高了1000倍,平均检测限达到飞摩尔范围。然而,综合毒性分析显示了显著的器官特异性风险:肝脏ROS生成(标准化平均差[SMD] = 1.42, 95% CI: 1.10-1.75)、肾小管凋亡(SMD = 1.27, 95% CI: 0.94-1.61)和β细胞损伤(SMD = 1.18, 95% CI: 0.88-1.49)。由于清除动力学差、慢性炎症和不完整的调控框架,转化挑战仍然存在。纳米颗粒在精确诊断方面具有变革性潜力,但其临床应用需要对毒理学权衡有细致的了解。未来的研究必须集中在可生物降解和肾脏清除材料、机械指导设计策略、标准化毒理学方案和人工智能驱动的预测模型上。这篇综述提供了一个双重视角的框架,将诊断突破与生物安全要求结合起来,指导纳米医学的下一阶段走向安全有效的临床转化。
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引用次数: 0
Quality by design of ultra deformable nanovesicles loaded with flunarizine for brain targeting utilizing risk assessment and multivariate analytical methods 利用风险评估和多变量分析方法,设计装载氟桂利嗪的超可变形纳米囊泡用于脑靶向
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-12 DOI: 10.1016/j.onano.2025.100265
Mahmood A. Haiss, Shaimaa N. Abd Alhammid
The swiftly changing technological and regulatory environments in the development of pharmaceutical drugs require risk based approach that integrates multivariate analysis utilizing Quality by Design (QbD). Flunarizine, a poorly water-soluble calcium channel blocker utilized for migraine treatment, exhibits low bioavailability. Spanlastics, contemporary nonionic based surfactant nanovesicles, enhance medication penetration due to their fluidic nature. Consequently, we optimized flunarizine spanlastic nanovesicles (FNZ-SNVs) utilizing formulation by design principles and investigated the viability of nose-to-brain delivery for migraine management. Ishikawa diagram was utilized to identify the risk factors that may affect the critical quality attributes of FNZ-SNVs. The use of Plackett–Burman experimental design was employed to test eight distinct formula and process factors affecting vesicle size, zeta potential, vesicle deformability, and encapsulation efficiency. Utilizing Pareto charts, three critical parameters were identified: type of vesicle builder (Span 60), type of EA (Tween 60), and sonication duration. Three levels of these essential factors were tuned by formulation by design to minimize vesicle size and enhance encapsulation efficiency, and vesicle deformability of FNZ-SNVs. The optimized FNZ-SNVs exhibited a vesicle size of 95.5 nm, an encapsulation efficiency of 86%, a relative deformability of 4.8 minutes, and a dissolving efficiency of 90.2%. Consequently, the optimized formula was integrated into an insitu-gel (IG) and investigated for additional in vivo assessment, which demonstrated that the degree of FNZ-SIG intranasal delivered to the brain was significantly greater than that of the intravenous FNZ solution, exhibiting an exceptionally elevated drug targeting index (DTI) of 1.12 and (DTE%) 112.1. This study illustrates the successful implementation of risk management and Quality by Design (QbD) methodologies in the formulation of brain-targeting release of FNZ-SIGs.
药物开发中快速变化的技术和监管环境需要基于风险的方法,利用设计质量(QbD)集成多变量分析。氟桂利嗪是一种水溶性差的钙通道阻滞剂,用于偏头痛治疗,生物利用度低。西班牙塑料,当代非离子基表面活性剂纳米囊泡,由于其流体性质,增强药物渗透。因此,我们根据设计原则优化了氟桂利嗪弹性纳米囊泡(FNZ-SNVs)的配方,并研究了鼻到脑给药治疗偏头痛的可行性。石川图用于识别可能影响fnz - snv关键质量属性的风险因素。采用Plackett-Burman实验设计,考察8种不同的配方和工艺因素对囊泡大小、zeta电位、囊泡变形能力和包封效率的影响。利用帕累托图,确定了三个关键参数:囊泡构建器类型(Span 60), EA类型(Tween 60)和超声持续时间。通过配方设计调整这三个关键因素的水平,以减小fnz - snv的囊泡大小,提高囊泡的包封效率和囊泡变形能力。优化后的fnz - snv囊泡尺寸为95.5 nm,包封效率为86%,相对变形率为4.8 min,溶解效率为90.2%。因此,我们将优化后的配方整合到注射凝胶(IG)中,并进行了进一步的体内评估,结果表明,FNZ- sig经鼻给药到脑的程度显著高于静脉给药,药物靶向指数(DTI)异常升高,分别为1.12和112.1。本研究说明了风险管理和设计质量(QbD)方法在fnz - sig脑靶向释放制定中的成功实施。
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引用次数: 0
Snail-collagen/chitosan nanocomposite film with silver nanoparticles for antimicrobial and regenerative wound healing 蜗牛-胶原/壳聚糖纳米复合膜与银纳米粒子抗菌和再生伤口愈合
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-11 DOI: 10.1016/j.onano.2025.100264
Dina Mohamed Mahmoud , Mohamed Mahmoud Abdelfatah , Tamer Mohamed Mahmoud , Omiya Ali Hasan , Randa Mohammed Zaki , Obaid Afzal , Mostafa Asim Darwish , Mohamed G. Ewees , Mostafa Nasr Taha , Mahmoud Mohamed Omar
Infected wounds pose a significant clinical challenge, driving the need for advanced dressings that actively combat infection and promote healing. This study developed a novel bio-composite film by integrating silver nanoparticle-enhanced, metronidazole-loaded lipidic nanovesicles into a snail slime collagen-chitosan matrix. A Design of Experiment optimized lipidic nanovesicle formulation (loaded with metronidazole) (Lop) was fabricated and characterized (DLS, drug release). Silver nanoparticles (AgNPs) were incorporated to form optimized nanovesicle formulation incorporating Silver Nanoparticles (Lop-AgNPs), which were embedded into a snail slime collagen (SSC)-chitosan (CS) matrix to create the final Lop.M film (optimized bio-composite film (Lop-AgNPs in a Snail Slime Collagen-Chitosan matrix). The film was tested for physicochemical properties, antimicrobial activity (disc diffusion), and efficacy in a rat wound model. The optimized formulation (Lop) showed a vesicle size of 339.5 ± 3.1 nm, zeta potential of -58.2 ± 2.8 mV, and entrapment efficiency of 88.6 ± 4.5% w/w, with 45.9 ± 3.2% w/w cumulative metronidazole release after 4 h. Upon silver incorporation, vesicle size increased to 358.9 ± 5.7 nm and zeta potential to -62.1 ± 3.2 mV. The composite film (Lop.M) exhibited a swelling index (SI) of 18.2 ± 0.4% w/w, film thickness of 0.71 ± 0.05 mm, and folding endurance > 50 folds. Antimicrobial zones of inhibition reached 50 mm for P. aeruginosa and 45 mm for Escherichia coli. In vivo, Lop.M-treated wounds demonstrated 96.4 ± 2.3% closure by day 14 compared to 68.1 ± 3.8% in controls. The Lop.M film, which demonstrated 96.4% wound closure in 14 days and potent antimicrobial activity, presents a strategy for wound management that combines robust antimicrobial action with active promotion of tissue regeneration.
感染的伤口是一个重大的临床挑战,推动需要先进的敷料,积极对抗感染和促进愈合。本研究通过将纳米银粒子增强、甲硝唑负载的脂质纳米囊泡整合到蜗牛黏液胶原-壳聚糖基质中,开发了一种新型生物复合膜。制备了含甲硝唑(Lop)的脂质纳米囊泡配方,并对其进行了表征(DLS,药物释放)。将银纳米颗粒(Lop-AgNPs)包埋在蜗牛黏液胶原蛋白(SSC)-壳聚糖(CS)基质中,形成最终的Lop纳米囊泡。M膜(优化的生物复合膜(蜗牛黏液胶原-壳聚糖基质中的Lop-AgNPs)。在大鼠伤口模型中测试了该膜的理化性质、抗菌活性(圆盘扩散)和功效。最佳配方(Lop)的囊泡大小为339.5±3.1 nm, zeta电位为-58.2±2.8 mV,包封效率为88.6±4.5% w/w, 4 h后甲硝唑的累积释放量为45.9±3.2% w/w。加入银后,囊泡大小增加至358.9±5.7 nm, zeta电位为-62.1±3.2 mV。复合膜(lopm)的膨胀指数(SI)为18.2±0.4% w/w,膜厚为0.71±0.05 mm,可折叠50次。铜绿假单胞菌和大肠杆菌的抑菌区分别为50 mm和45 mm。在体内,Lop。m治疗的伤口在第14天愈合率为96.4±2.3%,而对照组为68.1±3.8%。垂下的。M膜在14天内显示出96.4%的伤口愈合和有效的抗菌活性,提出了一种将强大的抗菌作用与积极促进组织再生相结合的伤口管理策略。
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引用次数: 0
Chitosan-functionalized selenium nanoparticles for targeted cancer therapy: Advances in synthesis, stability, and tumor-specific delivery 靶向癌症治疗的壳聚糖功能化硒纳米颗粒:合成、稳定性和肿瘤特异性递送的进展
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-11-01 DOI: 10.1016/j.onano.2025.100263
Tubagus Akmal , Yedi Herdiana , Ahmed Fouad Abdelwahab Mohammed , Safwat A. Mahmoud , Khaled M. Elamin , Gofarana Wilar , Nasrul Wathoni
Chitosan-functionalized selenium nanoparticles (CS-SeNPs) integrate selenium’s redox-active anticancer potential with chitosan’s stabilization, mucoadhesion, and ligand-ready surface to enable tumor-selective delivery. This review consolidates advances in chemical, physical, and green syntheses; relates processing to size, charge, colloidal stability, and drug loading; and maps these attributes to biodistribution, cellular uptake, and controlled release. Emphasis is placed on modified chitosan derivatives that confer pH or redox responsiveness, enhanced permeability and retention, active targeting, and co-delivery of chemotherapeutics or photosensitizers. Anticancer mechanisms encompass mitochondrial apoptosis, ROS modulation, cell-cycle arrest, anti-metastatic activity, and chemo- or photo-synergy. A critical comparison with metal-oxide platforms and discussion of environmental fate, biofilm reactor data, hemocompatibility, and immunotoxicity delineate benefits and remaining risks. Key translational priorities include scalable green synthesis, robust physicochemical and release specifications, in vivo exposure–response models, and regulatory-grade safety packages. CS-SeNPs thus represent a credible path toward precision oncology.
壳聚糖功能化硒纳米颗粒(CS-SeNPs)将硒的氧化还原活性抗癌潜力与壳聚糖的稳定性、黏附性和配体表面结合起来,实现肿瘤选择性递送。本文综述了化学、物理和绿色合成方面的进展;将处理与尺寸、电荷、胶体稳定性和药物装载联系起来;并将这些属性映射到生物分布,细胞摄取和控制释放。重点放在修饰的壳聚糖衍生物,赋予pH或氧化还原反应性,增强渗透性和保留性,主动靶向和化疗药物或光敏剂的共同递送。抗癌机制包括线粒体凋亡、ROS调节、细胞周期阻滞、抗转移活性以及化学或光协同作用。与金属氧化物平台的关键比较以及对环境命运、生物膜反应器数据、血液相容性和免疫毒性的讨论描绘了益处和剩余的风险。关键的翻译优先事项包括可扩展的绿色合成,强大的物理化学和释放规范,体内暴露反应模型和监管级安全包装。因此,CS-SeNPs代表了一条通向精确肿瘤学的可靠途径。
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引用次数: 0
Phytochemical-capped silver nanoparticles from the medicinal plant Embelia laeta disrupting 3D tumorspheres and inducing ROS-mediated apoptosis in MCF-7 breast cancer cells 来自药用植物叶红的植物化学覆盖银纳米颗粒破坏3D肿瘤球并诱导ros介导的MCF-7乳腺癌细胞凋亡
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-10-18 DOI: 10.1016/j.onano.2025.100262
Thi Thanh Huong Le , Van Hung Hoang , Thi Quynh Nguyen , Dac Trung Nguyen , Viet Hoang , Thu Huong Trinh , Thi Tam Khieu , Phu Hung Nguyen
Plant-based green nanotechnology provides a promising strategy that integrates phytochemicals with metallic nanoparticles for targeted cancer therapy. In this study, silver nanoparticles (Eml-AgNPs) synthesized using Embelia laeta (L.) Mez. leaf extract were investigated for their anticancer potential. The Eml-AgNPs were spherical, crystalline, and averaged 13.4 ± 4.6 nm in size, as confirmed by UV–Vis spectroscopy (absorption peak at 453 nm), XRD, FTIR, and TEM analyses. UPLC-QToF-MS profiling revealed 13 bioactive molecules bound to the nanoparticle surface, contributing to their stability and anticancer efficacy. Eml-AgNPs demonstrated potent, concentration-dependent cytotoxicity against HepG2, AGS, MCF-7, and MKN45 cancer cell lines, with IC₅₀ values ranging from 0.78 µg/mL to 1.67 µg/mL. In 3D tumorsphere cultures, treatment with Eml-AgNPs (2–5 µg/mL) significantly disrupted spheroid morphology and cellular cohesion. Mechanistic studies indicated ROS-mediated apoptosis, evidenced by a 36.7 % increase in Annexin V-FITC-positive cells (p < 0.01) and a 32.7 % elevation in ROS generation following treatment with 5 µg/mL Eml-AgNPs (p < 0.01). Furthermore, expression of pro-apoptotic genes including CASP8, CASP9, GADD45, and BAX was significantly upregulated. Collectively, these findings highlight the potential of Eml-AgNPs as a green nanotherapeutic platform, leveraging phytochemical synergy to induce oxidative stress-driven apoptosis in cancer cells. Further in vivo studies are needed to confirm the efficacy and safety of Eml-AgNPs for potential biomedical applications.
基于植物的绿色纳米技术提供了一种很有前途的策略,将植物化学物质与金属纳米粒子结合起来用于靶向癌症治疗。在本研究中,银纳米粒子(Eml-AgNPs)是由Eml-AgNPs合成的。Mez。研究了叶提取物的抗癌作用。通过紫外可见光谱(吸收峰在453nm处)、XRD、FTIR和TEM分析证实,Eml-AgNPs为球形结晶,平均尺寸为13.4±4.6 nm。UPLC-QToF-MS分析显示,13种生物活性分子结合在纳米颗粒表面,有助于其稳定性和抗癌功效。Eml-AgNPs对HepG2, AGS, MCF-7和MKN45癌细胞系表现出有效的浓度依赖性细胞毒性,IC₅0值范围为0.78 μ g/mL至1.67 μ g/mL。在3D肿瘤球培养中,Eml-AgNPs(2-5µg/mL)显著破坏了球体形态和细胞内聚。机制研究表明ROS介导的细胞凋亡,Annexin v - fitc阳性细胞增加36.7% (p < 0.01), 5µg/mL Eml-AgNPs处理后ROS生成增加32.7% (p < 0.01)。此外,促凋亡基因CASP8、CASP9、GADD45和BAX的表达显著上调。总之,这些发现突出了Eml-AgNPs作为绿色纳米治疗平台的潜力,利用植物化学协同作用诱导癌细胞氧化应激驱动的细胞凋亡。需要进一步的体内研究来证实Eml-AgNPs在潜在生物医学应用中的有效性和安全性。
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