Poly-L-glutamic acid derivatives as vectors for gene therapy.
This paper describes the synthesis and evaluation of biodegradable derivatives of poly-L-glutamic acid as suitable vectors for gene therapy. When mixed with DNA the new polymers self assemble and form polyelectrolyte complexes. The formation of the complexes and determination of their stability towards disruption by serum albumin was monitored by Ethidium bromide (EtBr) fluorescence spectroscopy. All polymers were able to form complexes and their size, determined by photon correlation spectroscopy, was between 84.5+/-2 nm and 96. 7+/-1.6 nm, depending on the type of polymer and the charge ratio. All complexes were stable towards serum albumin. The results from the biodegradability tests, using tritosomes, show that the polymers are biodegradable and the rate of degradation is influenced by the number of charged groups in the side chains. Haemolysis and red blood cell (RBC) agglutination were assessed and compared to poly(L-lysine) (pLL) and polyethyleneimine (pEI). RBC agglutination was monitored with optical microscopy. Results show that the new polymers are less toxic than pLL and pEI. Preliminary transfection studies show that the polymers are suitable vectors for gene delivery.
Dekie
L
L
Polymer Materials Research Group, Department of Organic Chemistry, University of Ghent, Ghent, Belgium.
Toncheva
V
V
Dubruel
P
P
Schacht
E H
EH
Barrett
L
L
Seymour
L W
LW
D015502:Absorptiometry, Photon; D000371:Agglutination / Q000187:drug effects; D000588:Amines / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004912:Erythrocytes / Q000187:drug effects; D004996:Ethidium / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008422:Materials Testing; D010316:Particle Size; D011099:Polyglutamic Acid / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis; D011725:Pyridines / Q000737:chemistry; D014162:Transfection
D000588:Amines; D005456:Fluorescent Dyes; D011108:Polymers; D011725:Pyridines; D011099:Polyglutamic Acid; D004996:Ethidium