脂质体面临的聚乙二醇_窘境_及其解决方法_张迪概述.pdfVIP

252 Acta Pharmaceutica Sinica 2015, 50 (3): 252?260 1, 1*, 1, 2 (1. , 116029; 2. , 110016) : (polyethylene glycol, PEG) , PEG , PEG PEG blood clearance, ABC) , PEG (PEG dilemma) PEG PEG pH PEG , PEG PEG PEG : ;; ; : R943.4 : A : 0513-4870 (2015) 03-0252-09 , pH (accelerated PEG “PEG dilemma” for liposomes and its solving approaches ZHANG Di1, XU Huan1*, HU Mei-na1, DENG Yi-hui2 (1. College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China; 2. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China) Abstract: Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor “endosomal escape” of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the “PEG dilemma”. “PEG dilemma” posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the “PEG dilemma”. This review focused on the definition, classification of “PEG dilemma”, and discussed several possible approaches to overcome “PEG dilemma”. Key words: polyethylene glycol; liposome; endosomal escape; accelerated blood clearance ? 20 90 , PEG (polyethylene glycol, PEG) , PEGPEG (PEGylated liposomes) , : 2014-07-31; : 2014-08-27. : ; (2013M530899). * Tel: 86-411 E-mail: huan.xu1@163.com , MPS) , (mononuclear phagocyte system, , [1, 2], (enhanced permeability and retention, EPR) 200 nm [3, 4] PEG , : , PEG (PEGylation) : PEG [5, 6]; PEG pH (pH-sensitive liposomes, PSL) (endosomal escape), [7, 8]; PEG (accelerated blood clearance, ABC) [9, 10], PEG (PEG dilemma)[11?14] PEG PEG PEG , PEG , PEG PEG 1 PEG 1.1 PEG , [