In silico and in vivo toxicity assessment of cysteamine-modified nanoparticles: implications for pharmacotherapy application.

IF 2.7 4区医学 Q1 Pharmacology, Toxicology and Pharmaceutics

Toxicology Mechanisms and Methods Pub Date : 2025-09-02 DOI:10.1080/15376516.2025.2538128

Babatunde Alabi, Sodiq Kolawole Lawal, Samuel Oluwaseun Olojede, Amina Suleiman, Olamide Adesanya, Diana Odey Ochuole, Fisayo Nathaniel Ogunleye, Benneth Ben-Azu

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引用次数: 0

Abstract

Background: Given the increasing therapeutic potential of cysteamine (CYST) at appropriate doses and expert concerns regarding the toxicity of nanoparticles, this study aimed to assess the toxicity profile of both CYST and silver nanoparticles conjugated with cysteamine (CYST-AgNPs).

Methods: For the acute study, a 300 mg/kg starting dose of CYST (i.p administration) produced a toxic response in some mice (n = 3/group), and a 300 mg/kg beginning dose of CYST-AgNPs produced delayed mild toxicity. Lower doses of CYST and CYST-AgNPs (50, 100, and 200 mg/kg; n = 3/group) were administered (i.p) for further acute toxicological evaluation. The sub-acute toxicity test was conducted for 21 days, and female mice (n = 5/group) were divided into control, CYST (25 and 50 mg/kg), and CYST-AgNPs (25 and 50 mg/kg). AgNPs and CYST-AgNPs were characterized with FTIR spectroscopy, UV spectrophotometer, HR-TEM, and SEM-EDX. Blood samples were collected via cardiac puncture and processed according to the standard hematological analysis protocols.

Results: The UV-vis absorbance wavelength range of 400-800 nm was observed. HR-TEM showed mostly spherical nanoparticles ranging from 30 to 90 nm. FTIR showed a functional group of O-H, C = C stretching vibration for AgNPs and O-H, S-H, N-H, C = C stretching vibration for CYST-AgNPs. EDX spectroscopy showed silver, carbon, oxygen, sodium, and chloride elements for AgNPs and CYST-AgNPs. The CYST decreased the WBC, RBC, and platelet counts significantly (p < 0.05), while CYST-AgNPs (25 and 50 mg/kg) reduced only the RBC counts (p < 0.05).

Conclusion: This investigation presents the in vivo safety analysis and pharmacological potential of cysteamine-modified silver nanoparticles (CYST-AgNPs), suggesting enhanced therapeutic activity.

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半胱氨酸修饰纳米颗粒的体内和硅毒性评估：对药物治疗应用的影响。

背景：鉴于半胱胺（囊肿）在适当剂量下的治疗潜力越来越大，以及专家对纳米颗粒毒性的担忧，本研究旨在评估囊肿和与半胱胺结合的银纳米颗粒（CYST- agnps）的毒性。方法：在急性研究中，300 mg/kg的囊肿起始剂量（腹腔给药）在一些小鼠（n = 3/组）中产生毒性反应，300 mg/kg的CYST- agnps起始剂量产生延迟性轻度毒性。低剂量的囊肿和CYST- agnps（50、100和200 mg/kg； n = 3/组）给予（i.p）进一步的急性毒理学评价。亚急性毒性试验21 d，雌性小鼠（n = 5/组）分为对照组、CYST- agnps（25、50 mg/kg）和CYST- agnps（25、50 mg/kg）。AgNPs和CYST-AgNPs用FTIR、UV、HR-TEM和SEM-EDX进行了表征。通过心脏穿刺采集血液样本，并根据标准血液学分析方案进行处理。结果：观察到紫外可见吸收波长范围为400 ~ 800 nm。HR-TEM显示的纳米颗粒大多为球形，粒径在30 ~ 90 nm之间。FTIR显示AgNPs为O-H， C = C伸缩振动官能团，CYST-AgNPs为O-H， S-H, N-H, C = C伸缩振动官能团。EDX光谱显示AgNPs和CYST-AgNPs存在银、碳、氧、钠和氯元素。结论：本研究提供了半胱氨酸修饰银纳米粒子（CYST- agnps）的体内安全性分析和药理潜力，表明其具有增强的治疗活性。

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来源期刊

Toxicology Mechanisms and Methods 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment.