PEGylated quaternized copolymer/DNA complexes for gene delivery

Abstract

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 ε-caprolactone and quaternized ε-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 50 kDa. 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.

Biodegradable poly(ɛ-caprolactone)–poly(ethylene glycol) copolymers as drug delivery system

“…Many approaches are being explored to improve the efficiency of non-viral gene delivery systems, seeking for different carrier formulations for plasmid DNA delivery. The PCL/PEG copolymers were intensively studied for its potential to be non-vial gene carriers Vroman et al, 2007;Huang et al, 2008). Research aimed at optimizing the carrier properties of PCL/PEG micro/nanoparticles has been reported.…”

“…Cytotoxicity, transfection efficiency and cellular uptake were significantly reduced relative to unshielded copolymer/DNA complexes. In conclusion, the PEGylated formulations might be an attractive approach for the in vivo application (Vroman et al, 2007). Furthermore, to reveal the effect of charge on the vehicle properties for systemic gene delivery, two types of MPEG-PCL nanoparticles containing pGL3-Control (plasmid DNA) were prepared using nonionic amphiphilic block copolymers and ionic amphiphilic block copolymers containing a terminal cationic group.…”

Macromolecular engineering and stimulus response in the design of advanced drug delivery systems

“…6 As an example, these degradable polycations have been used to generate complexes with negatively charged DNA for novel gene delivery systems. 7 More recent research has exploited "click chemistry," in which either a-chloro or g-bromo substituents of copolyesters are fi rst converted into azides. This is followed by the Huisgens 1,3-dipolar addition of functional alkynes, particularly alkynes bearing either a hydroxyl group, a carboxylic acid, or a tertiary amine (quaternized or not).…”

Macromolecular Engineering of Biodegradable Polyesters by Ring‐Opening Polymerization and ‘Click’ Chemistry

“…Cationic aliphatic polyesters were recently investigated as DNA vectors in gene therapy 42–44. Their synthesis is an additional convincing example of the superiority of CuAACs over more traditionally used reactions.…”