摘要
目的:系统总结当前纳米药物粒径测定的主要方法,分析其技术原理、适用范围及局限性,为纳米药物的研发、生产与质量控制提供科学依据。方法:通过调研近年来国内外文献中采用的纳米药物粒径测定方法,综述并对比了多种纳米药物粒径测定技术,包括图像法(例如电子显微镜、荧光显微镜)、激光散射法(例如动态光散射、纳米颗粒跟踪分析)、沉降法(例如差示离心沉降)、电阻脉冲法(例如可调电阻脉冲传感技术),以及其他新兴技术(例如纳米流式细胞术、原子力显微镜、场流分离等)。根据分析模式的不同,进一步将这些方法归纳为集成式(群体平均)分析方法和单颗粒水平分析方法,并对比分析了二者的技术特点、适用范围和局限性。结果:集成式粒径测定方法具有操作简便、适于高通量初筛的优势,但通常仅提供平均粒径信息,可能掩盖多分散体系的复杂性;而单颗粒水平分析技术能够提供高精度的个体颗粒信息与详细的粒径分布,但普遍存在通量低、样品制备复杂等问题。不同方法在数据代表性与应用场景上具有显著差异,且存在明显的互补性。结论:在实际研究中,单一粒径测定方法往往难以全面反映纳米药物的粒径特征,推荐采用多技术联用的策略,结合集成式与单颗粒分析方法,实现对纳米药物粒径的精确、全面表征。此外,未来应进一步推动粒径测定技术的标准化流程建设、多技术数据融合与人工智能辅助分析,以提升纳米药物质量控制的科学性与可靠性,加速其临床转化与应用。
Objective:To systematically summarize the major methods currently used for particle size determination of nanomedicines,analyze their technical principles,applicable scopes,and limitations,and provide scientific basis for the research,development,production,and quality control of nanomedicines Methods:Through a comprehensive review of nanoparticle size determination methods reported in recent domestic and international literatures,this article summarized and compared a variety of techniques,including imaging-based methods(e.g.,electron microscopy,fluorescence microscopy),light scattering techniques(e.g.,dynamic light scattering,nanoparticle tracking analysis),sedimentation-based methods(e.g.,differential centrifugal sedimentation),coulter principle(e.g.,tunable resistive pulse sensing),as well as other emerging technologies(e.g.,nano-flow cytometry,atomic force microscopy,field-flow fractionation).Based on their analytical approaches,these methods were further categorized into ensemble-based(bulk-average)analysis methods and single-particle-level analysis methods,and their technical features,application scopes,and limitations were comparatively analyzed.Results:Ensemble-based methods were characterized by ease of operation and suitability for rapid high-throughput preliminary screening;however,they typically provided only average particle size information,which may obscure the complexity of polydisperse systems.In contrast,single-particle-level analysis techniques could deliver high-resolution,individual particle data and detailed particle size distributions,but were often limited by low throughput and complex sample preparation requirements.These methods differ significantly in terms of data representativeness and applicability,yet they also demonstrate strong complementarity.Conclusion:In practical research,a single nanoparticle size determination method is often insufficient to fully reflect the particle size characteristics of nanomedicines.It is therefore recommended to adopt a multi-technique strategy that combines ensemble-based and single-particlelevel approaches to achieve accurate and comprehensive characterization of nanoparticle size.Furthermore,future efforts should focus on establishing standardized protocols for particle size measurement,integrating multi-technique data,and leveraging artificial intelligence-assisted analysis,to enhance the scientific rigor and reliability of nanomedicine quality control and to accelerate their clinical translation and application.
作者
孙葭北
万方劼
吴昀
姚尚辰
Sun Jabei;Wan Fangjie;Wu Yun;Yao Shangchen(National Institutes for Food and Drug Control,Beijing 102629,China;Beijing Tide Pharmaceutical Co.,Ltd,Beijing 100176,China)
出处
《中国药事》
2025年第12期1434-1443,共10页
Chinese Pharmaceutical Affairs
基金
药品监管科学全国重点实验室课题(编号2023SKLDRS0109)
国家药品监督管理局药品监管科学体系建设重点项目(编号RS2024H005)资助项目。
关键词
纳米药物
表征
尺寸效应
粒径测定
单颗粒表征
nanomedicines
characterization
size effect
particle size determination
single-particle characterization
