1: Int J Pharm. 2007 Nov 1;344(1-2):88-95. Epub 2007 Jul 3.

PEGylated quaternized copolymer/DNA complexes for gene delivery.

Vroman B, Ferreira I, Jérôme C, Jérôme R, Préat V.

Université Catholique de Louvain, Unité de Pharmacie Galénique, Avenue E. Mounier
73.20, 1200 Brussels, Belgium.

The aim of this study was to improve the colloidal stability, decrease unspecific
interactions with cells and blood components of a novel gene delivery system
composed of varepsilon-caprolactone and quaternized varepsilon-caprolactone. For 
this purpose, diblock 50/50 copolymer was used to generate complexes with DNA by 
either the solvent evaporation technique and by dialysis. The size, surface
charge and degree of interaction of the plasmid-loaded formulations were
measured. Then, polyplexes were combined with a poly(CL)-b-PEG copolymer to
create a hydrophilic corona on the surface of the complexes. The cytotoxicity,
transfection efficiency and cellular uptake of polyplexes and their association
with PEG were evaluated on HeLa cells. The dialysis method did not allow to
reduce the size of complexes as compared to the solvent evaporation method. The
zeta potential of polyplexes became positive from a charge ratio of 4. The degree
of interaction of copolymer with plasmid DNA was very high. Cytotoxicity and
transfection efficiency were found to be comparable to polyethylenimine 50kDa.
Association of polyplexes with poly(CL)-b-PEG copolymer led to a small increase
in particle size and a sharp decrease of charge surface. Cytotoxicity,
transfection efficiency and cellular uptake were significantly reduced relative
to unshielded copolymer/DNA complexes. The PEGylated formulations may be an
attractive approach for an in vivo application.

PMID: 17689899 [PubMed - in process]

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