化工进展 ›› 2023, Vol. 42 ›› Issue (4): 2003-2012.DOI: 10.16085/j.issn.1000-6613.2022-1025
收稿日期:
2022-06-02
修回日期:
2022-08-19
出版日期:
2023-04-25
发布日期:
2023-05-08
通讯作者:
周明
作者简介:
李建雄(1977—),男,博士,研究方向为先进成形制造。E-mail:lijx@newhope.cn。
基金资助:
LI Jianxiong1,2(), GENG Shuang2, HU Shujian1, ZHOU Ming1()
Received:
2022-06-02
Revised:
2022-08-19
Online:
2023-04-25
Published:
2023-05-08
Contact:
ZHOU Ming
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。
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.
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 | |
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 |
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 |
表1 全球范围内获批上市和国内获批临床研究的脂质体
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 | |
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 |
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 |
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[1] | 刘源岗1,2,郑琪瑶1,王士斌1,2. 盐酸米托蒽醌多囊脂质体的制备工艺优化及性能[J]. 化工进展, 2013, 32(06): 1395-1400. |
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