Principles of Clinical and Engineering Integration in Hemocompatibility - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 22

balloon and the outer surface of the elongated member. Within the lumen, flex-
ible members can be disposed. The flexible members can have both an external
surface as well as an internal cavity that contains the therapeutic agent criti-
cal to the DEB activity. A connecting channel can network the outer surface of
the balloon with the internal cavity. The balloon is subjected to high pressures
when being inflated [73]. A 60-second drug-elution time can be anticipated
[60, 72].
Various materials may be used to construct the DEB. For the strands of the
DEB, a polymer blend, metal alloy, laminar or composite construction may be
used. Substances for the balloons and members with elongated materials used
include polytetrafluoroethylenes, polyethylenes, polypropylenes, polyure-
thanes, nylons, and polyesters (including polyalkylene terephthalate polymers
and copolymers). Therapeutic agents for treating restenosis include sirolimus,
tacrolimus, everolimus, cyclosporine, dexamethasone, paclitaxel, actinomycin,
geldanamycin, cilostazole, methotrexate, vincristine, and mitomycin [72, 73].
Several important discoveries have given rise to the use of local paclitaxel
delivery with through-coated balloons. First, sustained drug release is not
required for a long-term antiproliferative effect. Second, a rapid uptake of
paclitaxel by vascular smooth muscle cells occurs and can be retained for up
to 1 week, thereby allowing a prolonged antiproliferation. Third, paclitaxel
has a strong lipophilic nature for its retention to the vessel wall, making it an
important therapeutic agent for DEB [72, 74].
Several important advantages for DEB have been indicated by Waksman
et al. A homogenous drug transfer to the entire vessel wall along with a rapid
release of high concentrations of the drug has been observed. This transfer may
be sustained for up to a week in the vessel wall. It should be noted, however,
that such delivery has little impact on long-term healing. The absence of a poly-
mer may decrease chronic inflammation and the trigger for late thrombosis.
DEBs may assist in avoiding stent placement in bifurcations or small vessels.
This may minimize the abnormal flow patterns that may occur with a stent.
Local delivery of DEB may also reduce the overdependence on antiplatelet
therapy [72].
Several indications have been suggested for the use of DEB. An important
indication of the DEB, especially for paclitaxel-eluting balloons, would be
for the treatment of in-stent restenosis. Other indications for the use of DEB
include tortuous vessels, small vessels, or long diffuse calcified lesions, which
can result in stent fracture. In addition, obstructing scaffolding of major side
branches or in bifurcated lesions may be another indication of DEB [72, 77].
The efficacy of a paclitaxel-eluting balloon for the treatment of sirolimus-
eluting stent (SES) restenosis has been assessed by an important prospec-
tive single-blind randomized trial by Habara et al. with a follow-up time
of 6 months as the primary end-point. The trial consisting of a total of 50
patients with SES restenosis in which patients were randomly assigned to
either a paclitaxel group (n = 25) or a conventional balloon angioplasty group
(n = 25). An incidence of recurrent restenosis of 8.7% in the DEB group was