title: Tris[2-(acryloyloxy)ethyl]isocyanurate cross-linked low-molecular-weight polyethylenimine as gene delivery carriers in cell culture and dystrophic mdx mice.
abstract: Hyperbranched poly(ester amine)s (PEAs) were successfully synthesized by Michael addition reaction between tris[2-(acryloyloxy)ethyl]isocyanurate (TAEI) and low-molecular-weight polyethylenimine (LPEI, M(w) 0.8k, 1.2k, and 2.0k) and evaluated in vitro and in vivo as gene carriers. PEAs effectively condensed plasmid DNA with particle sizes below 200 nm and surface charges between 11.5 and 33.5 mV under tested doses [at the ratios 2-10:1 of polymer/pDNA(w/w)]. The PEAs showed significantly lower cytotoxicities when compared with PEI 25k in two different cell lines. The PEAs (C series) composed of PEI 2k showed higher transgene expression compared to PEAs of PEI 0.8k (A series) or 1.2k (B series). Highest gene transfection efficiency in CHO, C2C12 myoblast, and human skeletal muscle (HSK) cell lines was obtained with TAEI/PEI-2K (C12) at a ratio of 1:2. Both C12, C14(TAEI/PEI-2K at a ratio of 1:4) demonstrated 5-8-fold higher gene expression as compared with PEI 25k in mdx mice in vivo through intramuscular administration. No obvious muscle damage was observed with these new polymers. Higher transfection efficiency and lower toxicity indicate the potential of the biodegradable PEAs as safe and efficient transgene delivery vectors.
authors.affiliation: Department of Neurology, McColl-Lockwood Laboratory for Muscular Dystrophy Research, Neuromuscular/ALS Center, Carolinas Medical Center, 1000 Blythe Boulevard, Charlotte, North Carolina 28231, USA. mingxing.wang@carolinashealthcare.org
authors.forename: Mingxing
authors.initials: M
authors.lastname: Wang
authors.forename: Jay D
authors.initials: JD
authors.lastname: Tucker
authors.forename: Peijuan
authors.initials: P
authors.lastname: Lu
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.forename: Caryn
authors.initials: C
authors.lastname: Cloer
authors.forename: Qilong
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D004355:Drug Stability; D006493:Heparin / Q000378:metabolism; D006801:Humans; D051379:Mice; D018101:Mice, Inbred mdx; D008970:Molecular Weight; D009136:Muscular Dystrophies / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D014162:Transfection / Q000379:methods*; D014227:Triazines / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D014227:Triazines; C574335:tris(2-(acryloyloxy)ethyl)isocyanurate; D011094:Polyethyleneimine; D006493:Heparin; D004247:DNA; C004632:cyanuric acid