PEG shielded polymeric double-layered micelles for gene delivery

Funhoff, Arjen M.; Monge, Sophie; Teeuwen, Rosalie L. M.; Koning, Gerben A.; Schuurmans-Nieuwenbroek, N.M.E.; Crommelin, Daan J.A.; Haddleton, David M.; Hennink, Wim E.; Nostrum, Cornelus F. van

doi:10.1016/j.jconrel.2004.11.005

Cited by 59 publications

(52 citation statements)

References 34 publications

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“…In addition, the nanocompartmentalization by block copoly-mer micelles or vesicles containing biomolecular functionality may provide interesting properties that could lead to applications such as controlled drug or gene delivery. 29 As a continuation of previously published work, 5 we were interested in the effect of a complementary nucleobase functionality on the aggregation behavior of amphiphilic block copolymers. For this purpose, we have synthesized a series of well-defined poly(ethylene glycol) (PEG)-poly(adenine) and PEG-poly(thymine) block copolymers via ATRP and have studied the aggregation phenomena of both the separate block copolymers and a mixture of the polymers with complementary nucleobases.…”

Section: Introductionmentioning

confidence: 97%

Synthesis and assembly behavior of nucleobase‐functionalized block copolymers

Spijker

Dirks

Hest

2006

J. Polym. Sci. A Polym. Chem.

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Block copolymers consisting of a poly(ethylene glycol) chain and a thymine‐ or adenine‐functional polymethacrylate block have been prepared with atom transfer radical polymerization, and their aggregation behavior in an aqueous medium has been studied. Upon the mixing of the two block copolymers, the critical aggregation concentration increases in comparison with the critical aggregation concentration of the individual block copolymers. It has therefore been demonstrated that the amphiphilic behavior of this class of block copolymers is affected by the interaction between the complementary nucleobases, which leads to an unexpected increase in the hydrophilicity of the block copolymer ensemble.

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Section: Introductionmentioning

confidence: 97%

Synthesis and assembly behavior of nucleobase‐functionalized block copolymers

Spijker

Dirks

Hest

2006

J. Polym. Sci. A Polym. Chem.

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“…A frequently applied strategy to stabilize copolymer/DNA complexes and neutralize positive charges is to shield the outer surface of the complexes with hydrophilic and uncharged polymers (Funhoff et al, 2005). Association of polyplexes with PEG is advantageous: (i) it reduces the cytotoxicity of polymer/DNA complexes; (ii) PEG shields excess positive charges of polymer/DNA complexes, resulting in the reduction of unspecific interactions between polyplexes and blood components and cells; (iii) PEG can be used as a spacer between a targeting ligand and the polymeric carrier, which facilitates the access of the ligand to its receptor (Lee and Kim, 2005).…”

Section: Introductionmentioning

confidence: 99%

PEGylated quaternized copolymer/DNA complexes for gene delivery

Vroman

Ferreira

Jérôme

et al. 2007

International Journal of Pharmaceutics

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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.

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“…However, this strategy fails during in vivo experiments where serum proteins are unavoidably present. Another approach is to mix DNA and carrier in precise stoichiometric ratio so as to result in electro-neutral complexes (Funhoff et al, 2005). Along similar lines, zwitterionic (McManus et al, 2004) or anionic (Liang et al, 2005) lipids have been proposed in which binding between carrier and plasmid is dependant on hydrophobic forces and the presence of divalent cations such as Ca 2+ , Zn 2+ and Mg 2+ to screen the disruptive repulsion between like charges.…”

Section: Intracellular Barriers In Gene Therapy: Problems and Potentimentioning

confidence: 99%