title: Therapeutic Use of 3β-[N-(N',N'-Dimethylaminoethane) Carbamoyl] Cholesterol-Modified PLGA Nanospheres as Gene Delivery Vehicles for Spinal Cord Injury.
abstract: Gene delivery holds therapeutic promise for the treatment of neurological diseases and spinal cord injury. Although several studies have investigated the use of non-viral vectors, such as polyethylenimine (PEI), their clinical value is limited by their cytotoxicity. Recently, biodegradable poly (lactide-co-glycolide) (PLGA) nanospheres have been explored as non-viral vectors. Here, we show that modification of PLGA nanospheres with 3β-[N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) enhances gene transfection efficiency. PLGA/DC-Chol nanospheres encapsulating DNA were prepared using a double emulsion-solvent evaporation method. PLGA/DC-Chol nanospheres were less cytotoxic than PEI both in vitro and in vivo. DC-Chol modification improved the uptake of nanospheres, thereby increasing their transfection efficiency in mouse neural stem cells in vitro and rat spinal cord in vivo. Also, transgene expression induced by PLGA nanospheres was higher and longer-lasting than that induced by PEI. In a rat model of spinal cord injury, PLGA/DC-Chol nanospheres loaded with vascular endothelial growth factor gene increased angiogenesis at the injury site, improved tissue regeneration, and resulted in better recovery of locomotor function. These results suggest that DC-Chol-modified PLGA nanospheres could serve as therapeutic gene delivery vehicles for spinal cord injury.
authors.affiliation: Spine & Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea.|Department of Bioengineering, Clemson University, Clemson, South Carolina, United States of America.
authors.forename: So-Jung
authors.initials: SJ
authors.lastname: Gwak
authors.affiliation: Spine & Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yeomin
authors.initials: Y
authors.lastname: Yun
authors.affiliation: Spine & Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Do Heum
authors.initials: DH
authors.lastname: Yoon
authors.affiliation: Spine & Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Keung Nyun
authors.initials: KN
authors.lastname: Kim
authors.affiliation: Spine & Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yoon
authors.initials: Y
authors.lastname: Ha
mesh_terms: D000818:Animals; D001692:Biological Transport; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007278:Injections, Spinal; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity; D054118:Nanospheres / Q000737:chemistry; D018919:Neovascularization, Physiologic; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects; D011094:Polyethyleneimine / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013116:Spinal Cord / Q000098:blood supply / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D019076:Transgenes; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011094:Polyethyleneimine; D002784:Cholesterol
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