Background: Although controversially discussed, paclitaxel is the only
clinically proven drug that inhibits restenosis when released from drug-coated
balloons (DCBs). Limus drugs are currently being explored as alternatives. The
aim of the preclinical studies was to investigate drug candidates beyond
paclitaxel considered for balloon coating. Methods: Drugs were tested with
respect to dissolution in organic solvents, coating on balloons, and drug
transfer to the vessel wall. Inhibition of neointimal proliferation was tested in
the porcine model of coronary in-stent stenosis. Intravascular drug treatment was
achieved by DCBs at the time of stent implantation. Results: Coating had to be
adjusted for each drug. Doses on the balloons ranged from 1.0 to
8.6 g/mm balloon surface. Satisfactory amounts of drug
ranging from 5% to 29% of initial doses were transferred into the vessel wall.
Angiographic parameters such as late lumen loss (LLL) at 4 weeks did not show
reduction of in-stent neointimal proliferation by treatment with arsenic trioxide
(0.87 0.44 mm), betamethasone dipropionate (1.00 0.54 mm),
bortezomib (1.74 0.46 mm), green tea extract (1.24 0.51 mm),
fantolon, an epothilone (0.86 0.61 mm), methotrexate (1.09
0.72 mm), and thalidomide (1.59 0.55 mm) compared to treatment with
uncoated balloons (1.07 0.60 mm), while coatings with paclitaxel reliably
reduced in-stent stenosis (LLL = 0.36 0.25 mm). Conclusions: Despite the
proven antiproliferative and/or anti-inflammatory effect of the drugs, none of
the coatings significantly reduced LLL compared to uncoated balloons and thus,
based on the results presented here, none of the tested coatings may be
considered a substitute for the paclitaxel-based coatings currently in clinical
use.