title: Polyethyleneimine-lipid conjugate-based pH-sensitive micellar carrier for gene delivery.
abstract: A low molecular weight polyethyleneimine (PEI 1.8 kDa) was modified with dioleoylphosphatidylethanolamine (PE) to form the PEI-PE conjugate investigated as a transfection vector. The optimized PEI-PE/pDNA complexes at an N/P ratio of 16 had a particle size of 225 nm, a surface charge of +31 mV, and protected the pDNA from the action of DNase I. The PEI-PE conjugate had a critical micelle concentration (CMC) of about 34 μg/ml and exhibited no toxicity compared to a high molecular weight PEI (PEI 25 kDa) as tested with B16-F10 melanoma cells. The B16-F10 cells transfected with PEI-PE/pEGFP complexes showed protein expression levels higher than with PEI-1.8 or PEI-25 vectors. Complexes prepared with YOYO 1-labeled pEGFP confirmed the enhanced delivery of the plasmid with PEI-PE compared to PEI-1.8 and PEI-25. The PEI-PE/pDNA complexes were also mixed with various amounts of micelle-forming material, polyethylene glycol (PEG)-PE to improve biocompatibility. The resulting particles exhibited a neutral surface charge, resistance to salt-induced aggregation, and good transfection activity in the presence of serum in complete media. The use of the low-pH-degradable PEG-hydrazone-PE produced particles with transfection activity sensitive to changes in pH consistent with the relatively acidic tumor environment.
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.
authors.forename: Rupa R
authors.initials: RR
authors.lastname: Sawant
authors.forename: Shravan Kumar
authors.initials: SK
authors.lastname: Sriraman
authors.forename: Gemma
authors.initials: G
authors.lastname: Navarro
authors.forename: Swati
authors.initials: S
authors.lastname: Biswas
authors.forename: Riddhi A
authors.initials: RA
authors.lastname: Dalvi
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D000818:Animals; D016923:Cell Death; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D018014:Gene Transfer Techniques; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D008546:Melanoma, Experimental; D051379:Mice; D008823:Micelles; D018613:Microscopy, Confocal; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry*; D055672:Static Electricity; D014162:Transfection
chemical_list: D008055:Lipids; D008823:Micelles; D010714:Phosphatidylethanolamines; C094877:dioleoyl phosphatidylethanolamine; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA