Assessing bioavailability and the toxicity of resveratrol nanoparticles: Insights from an in vivo chicken embryonic model

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY Food and Chemical Toxicology Pub Date : 2025-06-01 Epub Date: 2025-03-14 DOI:10.1016/j.fct.2025.115390

Jinglin Zhang , Xinwen Zhang , Qin Wang , Changqing Wu

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Abstract

This study evaluates the bioavailability, developmental toxicity, genotoxicity, and estrogenic effects (EA) of resveratrol nanoparticles (NPs) stabilized by Tween 80 and carboxymethyl chitosan (CMCS) using chicken embryonic models. Tween NPs exhibited smaller sizes (93.18 nm), and more homogeneous distribution compared to CMCS NPs (267.92 nm). Resveratrol-loaded CMCS NPs achieved a peak serum concentration (Cmax) of 0.462 μg/mL at 60 min, while Tween NPs showed lower bioavailability (Cmax = 0.16 μg/mL). CMCS NPs induced a higher mortality (45.0 %) at 760 μg/kg compared to Tween NPs (25.0 %) and resveratrol (0 %). Without loaded with resveratrol, Tween Empty NPs and CMCS Empty NPs showed higher mortality (51.5 % and 60.7 %, respectively). As capping agents, Tween 80 showed minimal mortality but induced malformation of 15.8 % at higher dose. CMCS increased mortality (30 %) and malformation (10 %) at 10 mg/kg. Empty NPs induced higher lipoperoxidation and DNA damage than resveratrol-loaded NPs. Tween Empty NPs significantly elevated DNA damage (p < 0.0001), while CMCS Empty NPs exhibited no genotoxic effects. Estrogen-responsive apolipoprotein II (ApoII) gene expression was significantly upregulated in the Tween Empty group (9.51 ± 3.27-fold), indicating potential EA of the nanocarrier. These findings highlight both the NPs and nanocarriers must be evaluated in safety of nano-formulations.

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评估白藜芦醇纳米颗粒的生物利用度和毒性：来自鸡体内胚胎模型的见解。

本研究在鸡胚胎模型上评价了t80和羧甲基壳聚糖稳定的白藜芦醇纳米颗粒（NPs）的生物利用度、发育毒性、遗传毒性和雌激素效应。与CMCS NPs （267.92 nm）相比，Tween NPs尺寸更小（93.18 nm），分布更均匀。白藜芦醇负载的CMCS NPs在60分钟的血清浓度峰值（Cmax）为0.462 μg/mL，而Tween NPs的生物利用度较低（Cmax = 0.16 μg/mL）。在760 μg/kg剂量下，CMCS NPs的死亡率（45.0%）高于Tween NPs（25.0%）和白藜芦醇（0%）。未加载白藜芦醇时，Tween Empty NPs和CMCS Empty NPs的死亡率更高（分别为51.5%和60.7%）。Tween 80作为封顶剂，在高剂量下死亡率极低，但致畸率为15.8%。CMCS在10 mg/kg时增加死亡率（30%）和畸形（10%）。与白藜芦醇负载的NPs相比，空NPs诱导更高的脂质过氧化和DNA损伤。Tween Empty NPs显著增加DNA损伤（p < 0.0001），而CMCS Empty NPs没有表现出遗传毒性作用。雌激素响应型载脂蛋白II （ApoII）基因表达在Tween Empty组显著上调（9.51±3.27倍），提示纳米载体的潜在EA。这些发现强调了纳米粒子和纳米载体必须在纳米制剂的安全性方面进行评估。

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.