title: Poly(ester amine) constructed from polyethylenimine and pluronic for gene delivery in vitro and in vivo.
abstract: A series of poly (ester amines) (PEAs) constructed from low molecular weight polyethyleneimine (LPEI, Mw: 0.8k, 1.2k Da) and Pluronic (different molecular weight (Mw) and hydrophilic-lipophilic-balance (HLB)) components were synthesized, and evaluated in vitro and in vivo as gene delivery carriers. Most PEA polymers were able to bind and condense plasmid DNA effectively into particles of approximately 150 nm in solution at the polymer/DNA ratio of 5 and above. Transfection efficiency of the PEA polymers depends on particle size of the polymer/DNA complex, molecular weight and HLB of the Pluronics and the size of PEI within PEA composition, as well as the cell type. Significant improvement in gene delivery efficacy was achieved with PEA01/04/05 composed of Pluronic size (Mw: 3000-5000 Da), and HLB (12-18) in CHO, C2C12 and HSkM cell lines; and the effective transfection was reflected with PEA 01/04/07 composed of Pluronics with size (2000-5000 Da) and HLB (12-23) in mdx mice. The best formulation for pDNA delivery was obtained with PEA 01 producing transgene expression efficiency 5, 19-folds of that of PEI 25k in vitro and in vivo, respectively. These results potent some of these PEA polymers as attractive vehicles for gene or oligonucleotide delivery.
authors.affiliation: a McColl-Lockwood Laboratory for Muscular Dystrophy Research, Carolinas Medical Center , Charlotte , NC , USA.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Wang
authors.affiliation: a McColl-Lockwood Laboratory for Muscular Dystrophy Research, Carolinas Medical Center , Charlotte , NC , USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: a McColl-Lockwood Laboratory for Muscular Dystrophy Research, Carolinas Medical Center , Charlotte , NC , USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Tucker
authors.affiliation: a McColl-Lockwood Laboratory for Muscular Dystrophy Research, Carolinas Medical Center , Charlotte , NC , USA.
authors.forename: Peijuan
authors.initials: P
authors.lastname: Lu
authors.affiliation: a McColl-Lockwood Laboratory for Muscular Dystrophy Research, Carolinas Medical Center , Charlotte , NC , USA.
authors.forename: Qilong
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003412:Cricetulus; D004247:DNA / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051379:Mice; D018101:Mice, Inbred mdx; D008970:Molecular Weight; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D020442:Poloxamer / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection / Q000379:methods
chemical_list: D011073:Polyamines; D011091:Polyesters; C516446:poly(caprolactone-block-ethyleneimine); D020442:Poloxamer; D011094:Polyethyleneimine; D004247:DNA
keywords: Amphiphilic cationic polymers; Pluronic; muscular dystrophy; non-viral gene delivery; polyethyleneimine