Supramolecular gene delivery vectors showing enhanced transgene expression and good biocompatibility.
Soluble supramolecular inclusion complexes were formed by threading alpha-cyclodextrin (alpha-CD) molecules over poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone) (PCL) chains of ternary block copolymers of PEG, PCL and polyethylenimine (PEI). Characteristic shifts of PCL absorptions in FTIR, (1)H NMR and UV spectra strongly suggest that alpha-CD is threaded over PEG and PCL blocks. Due to the reduced hydrophobic interaction between PCL blocks, the resulting supramolecular complexes displayed a dramatically increased solubility, in comparison with the ternary block copolymers. Their ability to complex DNA was almost as efficient as that of branched PEI 25 kDa, as shown in the ethidium bromide fluorescence quenching experiments. Resulting DNA polyplexes displayed a size of around 200 nm and a neutral surface charge. Microscopy studies in 3T3 fibroblasts revealed an efficient cellular uptake. Transfection efficiencies of inclusion complexes were in the same order of magnitude as PEI. In contrast to PEI a 100x lower toxicity was observed by MTT-assay, allowing the administration of nitrogen-to-phosphate ratios of up to 20. These new gene delivery systems merit further characterization under in vivo conditions.
Shuai
Xintao
X
Department of Pharmaceutics and Biopharmacy, Philipps-University of Marburg, Ketzerbach 63, D-35032 Marburg, Germany.
Merdan
Thomas
T
Unger
Florian
F
Kissel
Thomas
T
D000818:Animals; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D046911:Macromolecular Substances / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051379:Mice; D041681:NIH 3T3 Cells; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D013057:Spectrum Analysis; D019076:Transgenes / Q000235:genetics; D047391:alpha-Cyclodextrins
D046911:Macromolecular Substances; D011091:Polyesters; D047391:alpha-Cyclodextrins; C016240:polycaprolactone; D011092:Polyethylene Glycols; D011094:Polyethyleneimine