Formulation and characterization of poly (D,L-lactide-co-glycolide) nanoparticle containing vascular endothelial growth factor for gene delivery.
OBJECTIVE
The stability, in vitro release, in vitro cell transfection efficiency and in vivo gene transfer of vascular endothelial growth factor (VEGF(165)) plasmid DNA-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles were investigated.


METHODS
DNA-loaded nanoparticles were prepared with PLGA bearing VEGF(165) plasmid DNA and characterized with respect to morphology, size and encapsulation efficiency. The gene transfer efficiency of nanoparticles was tested in vitro on the cultured myocardial cells. And then the suspension of VEGF-loaded nanoparticles (VEGF-NPs) was injected into myocardial tissues in vivo to observe the process of nanoparticles as vectors for gene transfer to cardiac myocytes and to detect its biological effect and evaluate angiogenesis.


RESULTS
The encapsulation efficiency of the VEGF-NPs was 58.06 +/- 2.8% and their diameter ranged 100-300 nm. VEGF gene could be successfully transfected into myocardial cells by nanoparticles, which significantly enhanced gene transfection efficiency. A great number of nanoparticles were seen in the myocardial cytoplasm and nucleus. Furthermore, the nanoparticles began to dissolve and degrade. There was a significant increase in the number of capillaries in the VEGF-NPs group when compared with the plasmid DNA group.


CONCLUSIONS
The PLGA nanoparticles are capable of DNA delivery to cardiac myocytes for treating ischaemic myocardium. The direct gene transfer of VEGF-NPs into ischaemic rabbit myocardium can improve cardiac function and increase the number of capillaries.
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 17 Changle West Road, Xi'an 710032, China.
F
F
Yi
H
H
Wu
G-L
GL
Jia
D000818:Animals; D002626:Chemistry, Pharmaceutical; D004247:DNA / Q000378:metabolism; D004337:Drug Carriers; D019344:Lactic Acid; D046529:Microscopy, Electron, Transmission; D017202:Myocardial Ischemia / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D049329:Nanostructures; D018919:Neovascularization, Physiologic; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000378:metabolism
D004337:Drug Carriers; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA