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介孔二氧化硅纳米颗粒静脉注射对小鼠的毒性评估:对药物递送的启示

Toxicity Assessment of Mesoporous Silica Nanoparticles upon Intravenous Injection in Mice: Implications for Drug Delivery.

作者信息

MacCuaig William M, Samykutty Abhilash, Foote Jeremy, Luo Wenyi, Filatenkov Alexander, Li Min, Houchen Courtney, Grizzle William E, McNally Lacey R

机构信息

Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA.

Department of Biomedical Engineering, University of Oklahoma, Norman, OK 73109, USA.

出版信息

Pharmaceutics. 2022 Apr 30;14(5):969. doi: 10.3390/pharmaceutics14050969.

Abstract

Nanoparticles are popular tools utilized to selectively deliver drugs and contrast agents for identification and treatment of disease. To determine the usefulness and translational potential of mesoporous silica nanoparticles (MSNs), further evaluations of toxicity are required. MSNs are among the most utilized nano-delivery systems due to ease of synthesis, pore structure, and functionalization. This study aims to elucidate toxicity as a result of intravenous injection of 25 nm MSNs coated with chitosan (C) or polyethylene glycol (PEG) in mice. Following acute and chronic injections, blood was evaluated for standard blood chemistry and complete blood count analyses. Blood chemistry results primarily indicated that no abnormalities were present following acute or chronic injections of MSNs, or C/PEG-coated MSNs. After four weekly administered treatments, vital organs showed minor exacerbation of pre-existing lesions in the 35KPEG-MSN and moderate exacerbation of pre-existing lesions in uncoated MSN and 2KPEG-MSN treatment groups. In contrast, C-MSN treatment groups had minimal changes compared to controls. This study suggests 25 nm MSNs coated with chitosan should elicit minimal toxicity when administered as either single or multiple intravenous injections, but MSNs coated with PEG, especially 2KPEG may exacerbate pre-existing vascular conditions. Further studies should evaluate varying sizes and types of nanoparticles to provide a better overall understanding on the relation between nanoparticles and in vivo toxicity.

摘要

纳米颗粒是用于选择性递送药物和造影剂以识别和治疗疾病的常用工具。为了确定介孔二氧化硅纳米颗粒(MSN)的实用性和转化潜力,需要进一步评估其毒性。由于易于合成、具有孔结构和可功能化,MSN是最常用的纳米递送系统之一。本研究旨在阐明静脉注射壳聚糖(C)或聚乙二醇(PEG)包被的25nm MSN对小鼠的毒性作用。在急性和慢性注射后,对血液进行标准血液化学和全血细胞计数分析。血液化学结果主要表明,急性或慢性注射MSN或C/PEG包被的MSN后未出现异常。在每周给药四次的治疗后,重要器官在35K PEG-MSN治疗组中显示出先前存在病变的轻微加重,在未包被的MSN和2K PEG-MSN治疗组中显示出先前存在病变的中度加重。相比之下,C-MSN治疗组与对照组相比变化最小。本研究表明,壳聚糖包被的25nm MSN单次或多次静脉注射时应引起最小的毒性,但PEG包被的MSN,尤其是2K PEG可能会加重先前存在的血管状况。进一步的研究应评估不同尺寸和类型的纳米颗粒,以更好地全面了解纳米颗粒与体内毒性之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec5b/9148138/dc2cbec8b148/pharmaceutics-14-00969-g001.jpg

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