Local delivery of an antiproliferative drug with use of hydrogel-coated angioplasty balloons.
OBJECTIVE
To determine the feasibility of using hydrogel-coated angioplasty balloons to deliver drugs that inhibit vascular smooth muscle cell (VSMC) proliferation.


METHODS
In initial experiments, the tyrphostin RG-50872 (1 mumol/L) completely inhibited VSMC proliferation induced by platelet-derived growth factor (PDGF) in vitro when RG-50872 treatment preceeded PDGF exposure by 15 minutes. This inhibition was reversible and was not due to cell toxicity. In further experiments, hydrogel-coated and silicone-coated angioplasty balloons (2.5 mm in diameter by 20 mm in length) were coated with either 10 microL of RG-50872 (40 mmol/L in dimethyl sulfoxide [DMSO]) or DMSO vehicle, or were left uncoated. Afterward, each angioplasty balloon was inflated, submerged in 50 mL of culture media, and agitated for 2 minutes to promote drug release. Dilutions of this media were tested for their ability to inhibit VSMC proliferation.


RESULTS
All hydrogel-coated balloons (n = 5) released sufficient RG-50872 to inhibit PDGF-induced VSMC proliferation by 95% or more, whereas none of the silicone-coated balloons (n = 4) did. DMSO-treated and untreated balloons had no effect on proliferation.


CONCLUSIONS
These findings demonstrate that the hydrogel-coating on angioplasty balloons can take up and release sufficient RG-50872 to significantly inhibit smooth muscle cell proliferation. Further in vivo experiments are needed to determine if hydrogel-coated balloons can deliver sufficient RG-50872 to the arterial wall to affect VSMC proliferation.
Consigny
P M
PM
Department of Radiology, Thomas Jefferson University, Philadelphia, Pa.
Barry
J J
JJ
Vitali
N J
NJ
D000800:Angioplasty, Balloon / Q000295:instrumentation*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009570:Nitriles / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D010636:Phenols / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011092:Polyethylene Glycols; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011817:Rabbits; D012828:Silicones; D020032:Tyrphostins
D009570:Nitriles; D010636:Phenols; D010982:Platelet-Derived Growth Factor; D012828:Silicones; D020032:Tyrphostins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; C001784:SF 6847; D004247:DNA; D011505:Protein-Tyrosine Kinases; D004121:Dimethyl Sulfoxide