功能化脂质体的体内命运:应用与挑战

In vivo Fate of Functionalized Liposomes:Applications and Challenges

功能化脂质体可以改善药物的体内过程进而实现药物的高效递送,主要表现为增强药物吸收、改变药物分布使其富集于靶标处、降低药物消除以延长作用时间等特点,是目前纳米药物研究的热点方向之一,具有广阔的应用前景。查询国家药品监督管理局(NMPA)、美国食品药品监督管理局(FDA)及欧洲药品管理局(EMA)公布的药品信息发现,目前上市的脂质体药物较少,且国内品种以仿制药为主,除聚乙二醇化脂质体外,没有其他功能化脂质体获批上市,说明相对于发表的科研论文及专利,功能化脂质体的临床转化率处于较低水平。基于此,笔者拟查阅近年来国内外功能化脂质体的相关研究案例,梳理功能化脂质体的概念和类别,围绕体内命运探讨其在药物递送中的特点及应用优势,分析其临床转化率低的主要原因有初期研究缺乏临床思维、功能性材料的有效性和安全性问题、体内外评价方法欠佳及放大生产困难等,并提出加强各学科间交叉渗透以提高研究初期实验设计的合理性、着重考察功能性材料修饰密度及材料间相互作用、开发更为准确安全的脂质体体内外示踪技术、综合评价功能化脂质体递药性能、以低成本和简便性为导向的处方组成及制备工艺优化等可能的应对策略,以期为功能化脂质体及其他载体类纳米药物的研发提供参考。

Functionalized liposomes can improve the in vivo process of drugs to achieve high-efficiency delivery by enhancing drug absorption,changing drug distribution and reducing the elimination,which is one of the hotspots in nanomedicine research with broad application prospects.However,the drug information published by official websites of National Medical Products Administration(NMPA),the United States Food and Drug Administration(FDA),and the European Medicines Agency(EMA)shows that there are few liposomal products on the market,and the domestic varieties are mainly generic drugs.Excepting for polyethylene glycolized(PEGylated)liposomes,no other functionalized liposomes have been approved for marketing,which indicates that the clinical translation of functionalized liposomes remains at a low level.Therefore,the relevant reports of functionalized liposomes in recent years were reviewed in this paper,their application advantages and main challenges in preparation research and development were discussed based on the in vivo process,and their low clinical translation mainly because of the insufficient clinical thinking,safety and efficacy of functional materials,inaccurate in vitro and in vivo analysis methods and difficulty in scaling up production.Meanwhile,the possible strategies such as introducing the concept of clinical multi-function to improve clinical acuity,focusing on examining the modification density of functional materials and the interaction between the modified materials,evaluating the drug delivery performance of functionalized liposomes from multiple perspectives and scenarios,and conducting cost and convenience-oriented formulation composition and preparation process optimization were proposed in order to provide a reference for the development of functionalized liposomes and other carrier-based nanomedicines.