New poly(amidoamine)s containing disulfide linkages in their main chain

被引:116
作者
Emilitri, E [1 ]
Ranucci, E [1 ]
Ferruti, P [1 ]
机构
[1] Dipartimento Chim Organ & Ind, I-20123 Milan, Italy
关键词
degradation; functionalization of polymers; hydrophilic polymers; kinetics (polym.); poly(amidoamine)s; soluble drug carriers;
D O I
10.1002/pola.20599
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
Novel poly(amidoamine)s (PAAs) containing disulfide linkages regularly arranged along their backbones were synthesized by the stepwise polyaddition of 2-methylpiperazine to N,N'-bis(acryloyl)cystamine (BACy1) or N,N'-bis(acryloyl)-(L)cystine (BACy2). Both bisacrylamides had, in turn, been obtained by the reaction of acryloyl chloride with the corresponding amines. All the products were characterized with H-1 and C-13 NMR spectroscopy, and the average molecular weights of the polymers were determined by size exclusion chromatography. Both PAAs showed different solubility properties. In particular, PAA-Cy1, derived from BACy1, was sparingly soluble in water, whereas PAA-Cy2, derived from BACy2, was very soluble in aqueous media. The polymerization rates were investigated with 1H NMR spectroscopy. In both cases, the experimental data were consistent with pseudo-second-order kinetics. The calcu lated kinetic constants were 5.96 X 10(-3) and 5.90 X 10(-2) min(-1) L mol(-1) for the polyaddition of BACy1 and BACy2, respectively. The observed hydrolytic degradation rate of PAA-Cy2 in a pH 7.4 tris(hydroxymethyl)aminomethane (TRIS) buffer was comparable to that of conventional amphoteric PAAs, that is, PAAs containing carboxyl groups in their repeating unit. Degradation experiments carried out in the presence of 2-mercaptoethanol with both PAAs demonstrated that the disulfide groups contained in its repeating units were susceptible to reductive cleavage in the presence of thiols. (c) 2005 Wiley Periodicals, Inc.
引用
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页码:1404 / 1416
页数:13
相关论文
共 26 条
[1]   DETERMINATION OF FREE AND TOTAL HOMOCYSTEINE IN HUMAN-PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH FLUORESCENCE DETECTION [J].
ARAKI, A ;
SAKO, Y .
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1987, 422 :43-52
[2]   New coupling reagents for the preparation of disulfide cross-linked conjugates with increased stability [J].
Arpicco, S ;
Dosio, F ;
Brusa, P ;
Crosasso, P ;
Cattel, L .
BIOCONJUGATE CHEMISTRY, 1997, 8 (03) :327-337
[3]   ETHANOL DECREASES PLASMA SULFHYDRYLS IN MAN - EFFECT OF DISULFIRAM [J].
BURGUNDER, JM ;
NELLES, J ;
BILZER, M ;
LAUTERBURG, BH .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1988, 18 (04) :420-424
[4]   Use of new aminosugar derivatives as comonomers for the synthesis of glycosylated poly(amido-amines) [J].
Casali, M ;
Riva, S ;
Ferruti, P .
JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS, 2001, 16 (06) :479-491
[5]  
CAVALLI R, UNPUB
[6]   Amphoteric linear poly(amido-amine)s as endosomolytic polymers: Correlation between physicochemical and biological properties [J].
Ferruti, P ;
Manzoni, S ;
Richardson, SCW ;
Duncan, R ;
Pattrick, NG ;
Mendichi, R ;
Casolaro, M .
MACROMOLECULES, 2000, 33 (21) :7793-7800
[7]  
Ferruti P, 2002, MACROMOL RAPID COMM, V23, P332, DOI 10.1002/1521-3927(20020401)23:5/6<332::AID-MARC332>3.0.CO
[8]  
2-I
[9]   RECENT RESULTS ON FUNCTIONAL POLYMERS AND MACROMONOMERS OF INTEREST AS BIOMATERIALS OR FOR BIOMATERIAL MODIFICATION [J].
FERRUTI, P ;
RANUCCI, E ;
SARTORE, L ;
BIGNOTTI, F ;
MARCHISIO, MA ;
BIANCIARDI, P ;
VERONESE, FM .
BIOMATERIALS, 1994, 15 (15) :1235-1241
[10]  
Ferruti P, 1998, NATO ADV SCI I A-LIF, V300, P207