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Therapeutic Arteriogenesis via the Ultrasound‐Microbubble‐Targeted Delivery of Fibroblast Growth Factor‐2 (FGF‐2) Bearing Poly(Lactic‐Co‐Glycolic Acid) Nanoparticles
Author(s) -
Chappell John C,
Song Ji,
Klibanov Alexander L,
Price Richard J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1147.1
Subject(s) - arteriogenesis , plga , microbubbles , fibroblast growth factor , glycolic acid , chemistry , arteriole , biomedical engineering , ultrasound , lactic acid , pharmacology , medicine , cancer research , angiogenesis , biochemistry , microcirculation , receptor , radiology , biology , genetics , bacteria , in vitro
We are developing a therapeutic arteriogenesis strategy in which ultrasound (US) is used to activate intravenously injected contrast agent microbubbles (MBs) and facilitate the targeted delivery of co‐administered fibroblast growth factor‐2 (FGF‐2)‐bearing poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) to skeletal muscle. Two weeks after treatment in a mouse hindlimb ischemia model, gracilis adductor muscles (GMs) exhibited an 18% increase in arteriolar length density when compared to controls [bovine serum albumin (BSA) bearing NPs]. In addition, the maximum diameter of the posterior GM feed artery, a major collateral pathway, was significantly increased with treatment (FGF‐2=156.8±16.4 μm vs. BSA=100.8±8.7 μm), as were the maximum diameters of the transverse arteriolar trees (FGF‐2=52.9±2.4 μm vs. BSA=39.8±1.9 μm). We conclude that FGF‐2‐bearing PLGA NPs stimulate both new arteriole formation and the structural enlargement of existing arterioles following targeted delivery with US and MBs. These results support the use of US in conjunction with MB contrast agents as a platform for the minimally‐invasive delivery of pro‐arteriogenic nanomedicine. Supported by NIH HL74082 and AHA0555511U.