Improved stability of polycationic vector by dextran-grafted branched polyethylenimine

被引:100
作者
Tseng, WC [1 ]
Jong, CM [1 ]
机构
[1] Natl Taiwan Univ Sci & Technol, Dept Chem Engn, Taipei 106, Taiwan
关键词
D O I
10.1021/bm034083y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In vivo instability of a polycationic vector limits its efficacy after systemic administration. Conjugation of hydrophilic polymers with neutral charge onto polycationic vectors has been used to improve the stability by reducing the interactions between the vectors and the blood components, Such as serum albumin. In this study, dextrans of molecular weight 10 000 (dex-10000) and 1500 (dex-1500) were used to produce various degrees of grafting on linear and branched polyethylenimines (PEI), and the dextran-grafted polymers were used to prepare DNA-polymer complexes. The changes in size and in zeta-potential and the extent of DNA release after the exposure of the complexes to bovine serum albumin (BSA) were used to evaluate the stability of the complexes prepared at various ratios of DNA to polymer. Only the use of dextran-grafted branched PEI was found to be effective to improve the stability of the complexes in the presence of BSA. Dex-10000 was noted to provide a slightly better shielding than dex-1500 against the aggregation caused by BSA and helped maintain the sizes within 200 nm and the zeta-potentials close to neutral. It is thus concluded that the dextran-grafted branched PEI improved the stability of the DNA-polymer complexes and showed potential to conjugate with ligands for in vivo targeted gene delivery.
引用
收藏
页码:1277 / 1284
页数:8
相关论文
共 32 条
[1]   A VERSATILE VECTOR FOR GENE AND OLIGONUCLEOTIDE TRANSFER INTO CELLS IN CULTURE AND IN-VIVO - POLYETHYLENIMINE [J].
BOUSSIF, O ;
LEZOUALCH, F ;
ZANTA, MA ;
MERGNY, MD ;
SCHERMAN, D ;
DEMENEIX, B ;
BEHR, JP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) :7297-7301
[2]   Overcoming the nuclear barrier:: Cell cycle independent nonviral gene transfer with linear polyethylenimine or electroporation [J].
Brunner, S ;
Fürtbauer, E ;
Sauer, T ;
Kursa, M ;
Wagner, E .
MOLECULAR THERAPY, 2002, 5 (01) :80-86
[3]   Lactose-poly(ethylene glycol)-grafted poly-L-lysine as hepatoma cell-targeted gene carrier [J].
Choi, YH ;
Liu, F ;
Park, JS ;
Kim, SW .
BIOCONJUGATE CHEMISTRY, 1998, 9 (06) :708-718
[4]   In vivo delivery to tumors of DNA complexed with linear polyethylenimine [J].
Coll, JL ;
Chollet, P ;
Brambilla, E ;
Desplanques, D ;
Behr, JP ;
Favrot, M .
HUMAN GENE THERAPY, 1999, 10 (10) :1659-1666
[5]   Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene delivery [J].
Dash, PR ;
Read, ML ;
Barrett, LB ;
Wolfert, M ;
Seymour, LW .
GENE THERAPY, 1999, 6 (04) :643-650
[6]  
Erbacher P, 1999, J GENE MED, V1, P210
[7]   LIPOFECTION - A HIGHLY EFFICIENT, LIPID-MEDIATED DNA-TRANSFECTION PROCEDURE [J].
FELGNER, PL ;
GADEK, TR ;
HOLM, M ;
ROMAN, R ;
CHAN, HW ;
WENZ, M ;
NORTHROP, JP ;
RINGOLD, GM ;
DANIELSEN, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (21) :7413-7417
[8]   ExGen 500 is an efficient vector for gene delivery to lung epithelial cells in vitro and in vivo [J].
Ferrari, S ;
Moro, E ;
Pettenazzo, A ;
Behr, JP ;
Zacchello, F ;
Scarpa, M .
GENE THERAPY, 1997, 4 (10) :1100-1106
[9]   CLINICAL-STUDIES OF LIPOSOME-ENCAPSULATED DOXORUBICIN [J].
GABIZON, A ;
ISACSON, R ;
LIBSON, E ;
KAUFMAN, B ;
UZIELY, B ;
CATANE, R ;
BENDOR, CG ;
RABELLO, E ;
CASS, Y ;
PERETZ, T ;
SULKES, A ;
CHISIN, R ;
BARENHOLZ, Y .
ACTA ONCOLOGICA, 1994, 33 (07) :779-786
[10]   Potentiation of cationic liposome-mediated gene delivery by polycations [J].
Gao, X ;
Huang, L .
BIOCHEMISTRY, 1996, 35 (03) :1027-1036