Improved stability of polycationic vector by dextran-grafted branched polyethylenimine.
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 10000 (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.
Tseng
Wen-Chi
WC
Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan. tsengwc@ch.ntust.edu.tw
Jong
Chai-Min
CM
D004247:DNA / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D015316:Genetic Therapy; D011073:Polyamines / Q000737:chemistry; D000071228:Polyelectrolytes; D011094:Polyethyleneimine / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000378:metabolism
D004247:DNA; D003911:Dextrans; D004337:Drug Carriers; D011073:Polyamines; D000071228:Polyelectrolytes; D011094:Polyethyleneimine; D012710:Serum Albumin, Bovine