Copolymers of ε-caprolactone and quaternized ε-caprolactone as gene carriers

PEGylated quaternized copolymer/DNA complexes for gene delivery

“…Cytotoxicity and transfection efficiency were found to be comparable to polyethylenimine 50 kDa, a conventional polymer used in gene therapy (Vroman et al, 2007). However, the positive charges of the polyplexes might lead in vivo (i) to unspecific interactions with blood components and cells and (ii) to unstability (floculation/aggregation) at high ionic strength.…”

“…Synthesis of diblock 50/50 copolymer of ε-caprolactone and quaternized ε-caprolactone was performed by ringopening polymerization of CL and BrCL initiated by Al(O i Pr) 3 followed by quaternization with pyridine (Detrembleur et al, 2000a,b;Vroman et al, 2007). Poly(CL)-b-PEG copolymer was also synthesized by ringopening polymerization using triethyla-luminium as catalyst as previously described (Vangeyte and Jérôme, 2004).…”

“…However, the positive charges of the polyplexes might lead in vivo (i) to unspecific interactions with blood components and cells and (ii) to unstability (floculation/aggregation) at high ionic strength. Poly(CL-b-Py + CL) 50/50 diblock copolymer was chosen for the associations studies with poly(CL)-b-PEG copolymer according to three parameters: (i) the diblock structure is more adapted for the association with PEG copolymer than a random structure, (ii) it was shown that the particle size of diblock 50/50 copolymer incubated in serum was smaller than this for other copolymers tested (data not shown) and (iii) poly(CL-b-Py + CL) 50/50 copolymer was found to be less cytotoxic than poly(CL-b-Py+CL) 20/80 copolymer (Vroman et al, 2007). The plasmid-loaded formulations have been characterized by their size, surface charge and degree of interaction.…”

“…The main aim of this present study was to improve the colloidal stability and in vivo biodistribution of the novel gene delivery systems based on ε-caprolactone and quaternized ε-caprolactone (Detrembleur et al, 2000a,b;Vroman et al, 2007) by reducing the size and/or introducing a hydrophilic corona. Firstly, diblock 50/50 copolymer was used to generate complexes with DNA by either the solvent evaporation technique (Vroman et al, 2007) and by dialysis (Gaucher et al, 2005) By using the dialysis technique, it was expected to formulate polyplexes with a reduced size compared to the solvent evaporation technique.…”

“…Firstly, diblock 50/50 copolymer was used to generate complexes with DNA by either the solvent evaporation technique (Vroman et al, 2007) and by dialysis (Gaucher et al, 2005) By using the dialysis technique, it was expected to formulate polyplexes with a reduced size compared to the solvent evaporation technique. In the second part of the work, polyplexes were combined with a poly(CL)-b-PEG copolymer to create a hydrophilic corona on the surface of the complexes.…”