Therapeutic Use of 3β-[N-(N',N'-Dimethylaminoethane) Carbamoyl] Cholesterol-Modified PLGA Nanospheres as Gene Delivery Vehicles for Spinal Cord Injury

PloS One
So-Jung GwakYoon Ha

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 ...Continue Reading

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Citations

Oct 14, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yating SunChenguang Zhou
Feb 6, 2017·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Chaitanya R JoshiAnuja Ghorpade
Feb 3, 2019·Acta Biomaterialia·Qingzheng ZhangXuesi Chen
Aug 17, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiang-Yu LiuChao Fang

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Methods Mentioned

BETA
transfection
electrophoresis
ELISA
protein assay
PCR

Software Mentioned

Metamorph

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