Nanosphere-mediated delivery of vascular endothelial growth factor gene for therapeutic angiogenesis in mouse ischemic limbs.
Polymeric nanosphere-mediated gene delivery may sustain the duration of plasmid DNA (pDNA) administration. In this study, poly(lactic-co-glycolic acid) (PLGA) nanospheres were evaluated as a gene carrier. The pDNA-loaded PLGA nanospheres were formulated with high encapsulation efficiency (87%). The nanospheres sustained release of pDNA for 11 days. The released pDNA maintained its structural and functional integrity. Furthermore, the PLGA nanospheres showed lower cytotoxicity than polyethylenimine (PEI) in vitro and in vivo. The nanospheres with vascular endothelial growth factor (VEGF) gene were injected into skeletal muscle of ischemic limb model, and gene expression mediated by the PLGA nanospheres with VEGF gene was compared to that of PEI/pDNA or naked pDNA in vivo. PLGA nanosphere/pDNA had significantly higher VEGF expression levels in comparison to PEI/pDNA and naked pDNA at 12 days after administration. In addition, gene therapy using PLGA nanospheres resulted in more extensive neovascularization at ischemic sites than both naked pDNA and PEI/pDNA. These results indicated that PLGA nanosphere might be useful as a potential carrier for skeletal muscle gene delivery applications.
Kang
Sun-Woong
SW
Department of Chemical Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
Lim
Hee-Won
HW
Seo
Sang-Woo
SW
Jeon
Oju
O
Lee
Minhyung
M
Kim
Byung-Soo
BS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000493:pharmacokinetics; D005121:Extremities / Q000098:blood supply* / Q000601:surgery; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006016:Glycolates / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007097:Imines / Q000737:chemistry / Q000494:pharmacology; D007511:Ischemia / Q000628:therapy*; D019344:Lactic Acid; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D054118:Nanospheres / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010316:Particle Size; D011095:Polyethylenes / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D006016:Glycolates; D007097:Imines; D011095:Polyethylenes; D042461:Vascular Endothelial Growth Factor A; C505405:poly(ethylene imine); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA