PURPOSE: To determine the feasibility of using hydrogel-coated angioplasty balloons to deliver drugs that inhibit vascular smooth muscle cell (VSMC) proliferation. MATERIALS AND 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. CONCLUSION: 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.
PURPOSE: To determine the feasibility of using hydrogel-coated angioplasty balloons to deliver drugs that inhibit vascular smooth muscle cell (VSMC) proliferation. MATERIALS AND 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. CONCLUSION: 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.
Authors: Randolph W Seidler; Susanne Allgäuer; Susanne Ailinger; Andreas Sterner; Nagendu Dev; Dietmar Rabussay; Henri Doods; Martin C Lenter Journal: Pharm Res Date: 2005-09-22 Impact factor: 4.200