Chinese Bulletin of Life Sciences. Application of new generation of polyethylene glycol in antigen modification and drug delivery

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1 Chinese Bulletin of Life Sciences Vol. 16, No. 5 Oct., (2004) , R97; R914.2 A Application of new generation of polyethylene glycol in antigen modification and drug delivery BIAN Li-Hong 1, MEI Xing-Guo 2, ZHANG Yang-Pei 1 * (1 Institute of Blood Transfusion, Academy of Military Medical Sciences, Beijing , China; 2 Institute of Toxicology and Pharmacology, Academy of Military Medical Sciences, Beijing , China) Abstract: Polyethylene glycol () and its derivatives are a group of compounds with high molecular weight as well as excellent properties such as biocompatibility, non-toxicity and non-immunogenicity. It was widely used in the field of biomedical science. This review expounded history of development, characters of new generation of and purpose of modification, especially in the application of blood conversion and cell transplantation. The use of agent-carrying system based on modification in the drug sustained-release was also discussed. Key words: polyethylene glycol; antigen; drug; control release (polyethylene glycol ) (monomethoxypolyethylene glycol m) 200~8 000D 8 000D HO-(CH 2 CH 2 O) n - CH 2 -CH 2 -OH m CH 3 O-(CH 2 CH 2 O) n -CH 2 -CH 2 -OH (1) [1~4] N'N'- (2) (FDA) (2002CB713804) (1966 ) (1954 ) (1944 ) *

2 297 (3) (4) [5] Abuchowski -COOH (1) S S - - (-OSu) (2) S (3) S - SC-( -) BTC-( -) - - [7] - - m- N ( 12 kd) () [6] [8~10] 1 1 α- ε-, (, ), α- ε- 2 (ylation) m (molecule altering structure m chemistry MASC) - m [11] (1) (2) (3) (4) BzO--OH + HO--OH HO--OCH 3 + CH 3 O--OCH 3 (1)

3 298 (2) (3) (4) (1) (2) (3) m m N- C- m m Scott Hortin m O Bradley m- C m-btc( ) m-spa BTCm-BTC SPA-m-SPA m m-c m-btc m-spa BTC-m-BTC SPA-m-SPA [12] m (1) 2~3 5~10 10~100 (2) (3) (RES) m ABO m-btc ABO m-ald( ) m 2 -NHS(N- ) ph mmol/L m-btc 1 A B AB hrbc A B A B AB hrbc O hrbc m-btc m-btc α- (Gal α- 1,3-Gal) m-btc 1977 Abuchowski [5] m So T m γ- T B 1.5~2.0 m (1DDM) m 1 1DDM

4 299 m Yun Lee m-spa(m- ) m Dong [13] [17] Cavallaro (polyhydroxyethylaspartamide /PHEA) 3.2 [14~16] / B PHEA-- Balb/c 6 17 AUC 30 Das -PLA( ) 25%~30% 30 PLA ( ) s (DSPE) (-DSPE) FDA L- L- L- L- -DSPE 24 35% 10% 24 10% 50% 100 Enzon SOD -G-CSF (DPPE--COOH) 3.2.2

5 300 2 [19] ( ) ( ) α-2b ( ) α-2b+ ( ) α-2a+ ( ) α-2a ( ) ( ) ( ) - ( ) α-2b III II I PDGF-β II II / (Cremophor EL) 0.25 ug/ml Cremophor EL (1.36 ) Cremophor EL Cremophor EL Dosio [18] (2kD 5kD)m 3.6ml/h 2.9ml/h(2kD) 1.97ml/h 1.41ml/h(5kD) 4 30 [1] Herman S, Hooftman G, Schacht E. Poly(ethylene glycol) with reactive endgroups:i. Modification of proteins. J Bioact Compat Polym, 1995, 10: 145~187 [2] Roberts M J, Bentley M D, Harris J M. Chemistry for peptide and protein ylation. Adv Drug Delivery Rev, 2002, 54: 459~476 [3] Zalipsky S. Chemistry of polyethylene glycol conjugates with biologically active molecules. Adv Drug Delivery Rev, 1995, 16: 157~182 [4],,.., 2000, 1: 39~45 [5] Abuchowski A, McCoy J R, Palczuk NC, et al. Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. J Biol Chem, 1977, 252(11): 3582~3586

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