Sustained VEGF delivery via PLGA nanoparticles promotes vascular growth.
Technologies to increase tissue vascularity are critically important to the fields of tissue engineering and cardiovascular medicine. Currently, limited technologies exist to encourage angiogenesis and arteriogenesis in a controlled manner. In the present study, we describe an injectable controlled release system consisting of VEGF encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). The majority of VEGF was released gradually over 2-4 days from the NPs as determined by an ELISA release kinetics experiment. An in vitro aortic ring bioassay was used to verify the bioactivity of VEGF-NPs compared with empty NPs and no treatment. A mouse femoral artery ischemia model was then used to measure revascularization in VEGF-NP-treated limbs compared with limbs treated with naked VEGF and saline. 129/Sv mice were anesthetized with isoflurane, and a region of the common femoral artery and vein was ligated and excised. Mice were then injected with VEGF-NPs, naked VEGF, or saline. After 4 days, three-dimensional microcomputed tomography angiography was used to quantify vessel growth and morphology. Mice that received VEGF-NP treatment showed a significant increase in total vessel volume and vessel connectivity compared with 5 microg VEGF, 2.5 microg VEGF, and saline treatment (all P < 0.001). When the yield of the fabrication process was taken into account, VEGF-NPs were over an order of magnitude more potent than naked VEGF in increasing blood vessel volume. Differences between the VEGF-NP group and all other groups were even greater when only small-sized vessels under 300 mum diameter were analyzed. In conclusion, sustained VEGF delivery via PLGA NPs shows promise for encouraging blood vessel growth in tissue engineering and cardiovascular medicine applications.
Golub
Justin S
JS
Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr., Atlanta, GA 30332, USA.
Kim
Young-tae
YT
Duvall
Craig L
CL
Bellamkonda
Ravi V
RV
Gupta
Divya
D
Lin
Angela S
AS
Weiss
Daiana
D
Robert Taylor
W
W
Guldberg
Robert E
RE
D000818:Animals; D001011:Aorta / Q000254:growth & development; D001672:Biocompatible Materials; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000254:growth & development; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology; D019344:Lactic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014057:Tomography, X-Ray Computed; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use
D001672:Biocompatible Materials; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid