脂质体递送系统功能结构设计与应用研究进展

doi:10.16085/j.issn.1000-6613.2022-1025

摘要/Abstract

摘要：

脂质体是人工制备的中空微球，由胆固醇、磷脂及其衍生物组装而成。得益于多样化的磷脂组分、粒径和中空球形结构，综合一系列电学、力学、材料学、表界面学特点，脂质体拥有优异的生物相容性和代谢属性，并具有靶向性和微环境响应能力，在药物递送、疾病诊断、高端日化及功能食品开发等领域有广泛研究。脂质体最成功的应用方式是作为纳米生物医药递送系统，研究成果和成熟产品不断涌现。基于此，本文从脂质体分子组成、空间特性、电学特性、表界面力学等结构特征出发，明确脂质体功能化设计核心要点，即创新制备技术以提升载药量和包封率，通过表面修饰以加强目标部位富集，将外源物理刺激与结构设计结合以实现程序释药，增强穿膜能力以完成有效入胞。结合最新研究，本文对脂质体负载药物、核酸、疫苗等成分的临床应用情况进行总结。

关键词: 脂质体, 递送系统, 功能结构, 应用进展

Abstract:

Liposomes are artificially prepared hollow microspheres, which are assembled from cholesterol, phospholipids and their derivatives. Depending on the diversified phospholipid components, particle size and hollow spherical structure, and a series of electrical, mechanical, material and surface interface characteristics, liposomes have excellent biocompatibility and metabolic properties, targeting and microenvironment response ability. Liposomes have been widely studied in the fields of drug delivery, disease diagnosis, high-end daily chemicals and functional food development. Nano biomedical delivery system is the most successful application of liposomes. Research results and mature products continue to emerge. Based on this, starting from the structural characteristics such as liposome molecular composition, spatial characteristics, electrical characteristics and surface interface mechanics, this paper defines the core points of liposome functional design, innovating preparation technology to improve drug loading and entrapment efficiency, strengthening the enrichment of target sites through surface modification, combining exogenous physical stimulation with structural design to achieve programmed drug release and enhancing membrane penetrating ability to complete the effective entry of liposomes into cells. Combined with the latest research, this paper summarizes the clinical application of liposomes carrying drugs, nucleic acids, vaccines and other substances.

Key words: liposomes, delivery system, functional structure, application progress

中图分类号:

李建雄, 耿爽, 胡树坚, 周明. 脂质体递送系统功能结构设计与应用研究进展[J]. 化工进展, 2023, 42(4): 2003-2012.

LI Jianxiong, GENG Shuang, HU Shujian, ZHOU Ming. Research progress on functional structure design and application of liposome delivery system[J]. Chemical Industry and Engineering Progress, 2023, 42(4): 2003-2012.

图/表 3

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治疗领域	主要候选药品	适应证	公司	临床/上市	临床/上市时间
抗肿瘤	多柔比星	多种实体瘤	Alza	上市	1995-11
		乳腺癌	Elan Pharmaceuticals	上市	2000-07
		卡波西肉瘤	上海复旦张江	上市	2005-12
		多种实体瘤	石药中奇	上市	2008-12
		卡波西肉瘤	常州金源	上市	2011-02
		多种实体瘤	Celsion	临床Ⅲ期	2015-12
	紫杉醇	多种实体痛	绿叶思科	上市	2007-03
		乳腺癌	南京泛太	临床Ⅱ期	2015-05
		多种实体瘤	石药集团	临床Ⅲ期	2017-07
		多种实体瘤	上海天汇	临床Ⅰ期	2006-09
	伊立替康	转移性上皮膀胱癌	Ipsen	上市	2015-10
		胰腺癌	恒瑞医药	临床Ⅲ期	2013-09
		多种实体瘤	齐鲁制药	临床Ⅰ期	2016-08
		晚期实体瘤	绿叶制药	临床Ⅰ期	2017-03
		晚期实体瘤	科伦药业	临床Ⅰ期	2017-03
		晚期大肠癌	上海景峰	临床Ⅰ期	2017-09
	柔红霉素	卡波西肉瘤	NeXstar	上市	1996-04
	阿糖胞苷	恶性淋巴癌	Pacira	上市	1999-04
	阿糖胞苷/柔红霉素	急性粒细胞白血病	Jazz Pharmaceuticals	上市	2018-08
	长春新碱	急性髓细胞性白血病，黑色素瘤	Spectrum	上市	2012-08
	长春新碱	急性髓细胞性白血病	上海复旦张江	上市	2009-03
	和厚朴酚	晚期非小细胞肺癌	成都金瑞	临床Ⅰ期	2016-05
抗感染	两霉素B	真菌感柒	NcXstar	上市	1990-08
		真菌感染	上海上药新亚	上市	2003-08
		真菌感染	北京泰德	临床Ⅰ期	2015-08
		真菌感染	石药集团	临床Ⅲ期	2021-11
		真菌感染	台湾东洋	临床Ⅰ期	2017-05
麻醉	硫酸吗啡	术后疼痛	Pacira	上市	2004-05
麻醉	布尔卡因	术后疼痛	Pacira	上市	2011-10
心脑血管	前列地尔	下肢动脉硬化闭塞症	石药集团	临床Ⅱ期	2019-09

治疗领域	主要候选药品	适应证	公司	临床/上市	临床/上市时间
抗肿瘤	多柔比星	多种实体瘤	Alza	上市	1995-11
		乳腺癌	Elan Pharmaceuticals	上市	2000-07
		卡波西肉瘤	上海复旦张江	上市	2005-12
		多种实体瘤	石药中奇	上市	2008-12
		卡波西肉瘤	常州金源	上市	2011-02
		多种实体瘤	Celsion	临床Ⅲ期	2015-12
	紫杉醇	多种实体痛	绿叶思科	上市	2007-03
		乳腺癌	南京泛太	临床Ⅱ期	2015-05
		多种实体瘤	石药集团	临床Ⅲ期	2017-07
		多种实体瘤	上海天汇	临床Ⅰ期	2006-09
	伊立替康	转移性上皮膀胱癌	Ipsen	上市	2015-10
		胰腺癌	恒瑞医药	临床Ⅲ期	2013-09
		多种实体瘤	齐鲁制药	临床Ⅰ期	2016-08
		晚期实体瘤	绿叶制药	临床Ⅰ期	2017-03
		晚期实体瘤	科伦药业	临床Ⅰ期	2017-03
		晚期大肠癌	上海景峰	临床Ⅰ期	2017-09
	柔红霉素	卡波西肉瘤	NeXstar	上市	1996-04
	阿糖胞苷	恶性淋巴癌	Pacira	上市	1999-04
	阿糖胞苷/柔红霉素	急性粒细胞白血病	Jazz Pharmaceuticals	上市	2018-08
	长春新碱	急性髓细胞性白血病，黑色素瘤	Spectrum	上市	2012-08
	长春新碱	急性髓细胞性白血病	上海复旦张江	上市	2009-03
	和厚朴酚	晚期非小细胞肺癌	成都金瑞	临床Ⅰ期	2016-05
抗感染	两霉素B	真菌感柒	NcXstar	上市	1990-08
		真菌感染	上海上药新亚	上市	2003-08
		真菌感染	北京泰德	临床Ⅰ期	2015-08
		真菌感染	石药集团	临床Ⅲ期	2021-11
		真菌感染	台湾东洋	临床Ⅰ期	2017-05
麻醉	硫酸吗啡	术后疼痛	Pacira	上市	2004-05
麻醉	布尔卡因	术后疼痛	Pacira	上市	2011-10
心脑血管	前列地尔	下肢动脉硬化闭塞症	石药集团	临床Ⅱ期	2019-09