Targeted delivery of nanoparticles bearing fibroblast growth factor-2 by ultrasonic microbubble destruction for therapeutic arteriogenesis.
Therapeutic strategies in which recombinant growth factors are injected to stimulate arteriogenesis in patients suffering from occlusive vascular disease stand to benefit from improved targeting, less invasiveness, better growth-factor stability, and more sustained growth-factor release. A microbubble contrast-agent-based system facilitates nanoparticle deposition in tissues that are targeted by 1-MHz ultrasound. This system can then be used to deliver poly(D,L-lactic-co-glycolic acid) nanoparticles containing fibroblast growth factor-2 to mouse adductor muscles in a model of hind-limb arterial insufficiency. Two weeks after treatment, significant increases in both the caliber and total number of collateral arterioles are observed, indicating that the delivery of nanoparticles bearing fibroblast growth factor-2 by ultrasonic microbubble destruction may represent an effective and minimally invasive strategy for the targeted stimulation of therapeutic arteriogenesis.
Chappell
John C
JC
Department of Biomedical Engineering and Robert M. Berne Cardiovascular Research Center, Box 800500, Health System, Charlottesville, VA, 22908, USA.
Song
Ji
J
Burke
Caitlin W
CW
Klibanov
Alexander L
AL
Price
Richard J
RJ
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000494:pharmacology*; D006016:Glycolates / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid; D051379:Mice; D045423:Microbubbles; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects; D053758:Nanoparticles; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014465:Ultrasonics
D006016:Glycolates; D016222:Fibroblast Growth Factor 2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid