Poly-l-glutamic acid derivatives as multifunctional vectors for gene delivery. Part A. Synthesis and physicochemical evaluation.
This paper describes the synthesis and evaluation of a series of multifunctional poly-l-glutamic acid derivatives that can be used as vectors for gene delivery. They readily form polyelectrolyte complexes with DNA, resulting in a reduced surface charge and size of the DNA. The formation of a polymer-DNA complex and the stability toward serum albumin was analyzed by ethidium bromide fluorescence measurements and agarose gel retardation studies. Most polymers, except those with more than 80% imidazoles, are able to condense calf thymus DNA, thus forming complexes with sizes varying between 105 and 172 nm. The surface charge of the complexes was determined at different charge ratios by zeta potential measurements. The buffering properties of the polymers were determined via titration studies. The results show that the polymers are able to buffer the endosomal environment, although to a smaller extent than polyethyleneimine. The first part of this study is devoted to the synthesis and the physicochemical evaluation of the multifunctional polymers and their use as carriers for genetic information. The second part, to be published subsequently, discusses the biological evaluation of the polymers and their complexes with DNA.
Dubruel
Peter
P
Department of Organic Chemistry, Ghent University, Ghent 9000 Belgium.
Dekie
Luc
L
Schacht
Etienne
E
D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000592:standards; D004247:DNA / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000592:standards; D015316:Genetic Therapy / Q000379:methods*; D008422:Materials Testing; D009690:Nucleic Acid Conformation; D011099:Polyglutamic Acid / Q000138:chemical synthesis* / Q000737:chemistry
D001672:Biocompatible Materials; D004337:Drug Carriers; D011099:Polyglutamic Acid; D004247:DNA