Copolymers of epsilon-caprolactone and quaternized epsilon-caprolactone as gene carriers.
New copolymers of epsilon-caprolactone (CL) and gamma-bromo-epsilon-caprolactone quaternized by pyridine (Py+CL) were investigated as non-viral vectors for gene delivery. Copolymers with two molar compositions (50 Py+CL/50 CL and 80 Py+CL/20 CL), each with a diblock or a random structure, were used to prepare nanoparticulate complexes with DNA. Average size and surface charge of the complexes and extent of the complexation were measured. The DNA condensation by the copolymers was analysed by a gel retardation assay. Cytotoxicity and transfection efficiency of the copolymers were also evaluated in HeLa cells and compared with polyethylenimine 50 kDa. The size of the polyplexes was approximately 200 nm. The zeta potential first increased with the copolymer/DNA charge ratio and became positive for charge ratios in the 2-4 range depending on the type of copolymer. DNA was completely condensed within the nanoparticles and the degree of interaction was very high. Cytotoxicity and transfection efficiency were found to be comparable to polyethylenimine 50 kDa. The experimental results suggest that the novel copolymers can be used as novel gene delivery vectors.
Vroman
Benoît
B
Unité de Pharmacie Galénique, Université Catholique de Louvain, Avenue E. Mounier 73.20, 1200 Brussels, Belgium.
Mazza
Michaël
M
Fernandez
Manuela R
MR
Jérôme
Robert
R
Préat
Véronique
V
D002208:Caproates / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004247:DNA; D018390:Gene Targeting / Q000379:methods*; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D008156:Luciferases / Q000378:metabolism; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D011725:Pyridines / Q000737:chemistry / Q000633:toxicity; D014162:Transfection
D002208:Caproates; D007783:Lactones; D011725:Pyridines; C121056:caprolactone; D004247:DNA; D008156:Luciferases; C023666:pyridine