Biomedical Engineering Reference
In-Depth Information
(3) There is no sustained delivery of the drugs over many months, as is the case with
some DES.
(4) In all likelihood, the use of a DEB will not produce delayed endothelialization,
hence antiplatelet therapy may be stopped sooner.
(5) DEBs may offer the possibility of better lesion coverage.
Several companies are working on introducing DEBs to the market (Waksman and Pakala,
2009). The ones in advanced stages include Elutax
®
developed by Aachen Resonance in
Germany, Sequent
®
Please developed by Braun Melsungen AG, and DIOR
®
developed by
Eurocor AG. All of the balloons appear to be simply coated with drug solutions, perhaps
when expanded, and then deflated to entrap solid drug in pockets. A slight variation on
this theme is the addition of the main component of x-ray contrast medium, iopromide,
to act as a “matrix” for the paclitaxel. This hydrophilic matrix (used in the Sequent Please
balloon) apparently allows for more complete delivery of the drug from the balloon into
tissue (Scheller et al., 2004) and, consequently, better results in inhibiting restenosis in a
porcine coronary artery model compared with paclitaxel trapped on roughened balloon
surfaces (Cremers et al., 2009).
Clinical studies with DEBs have been very encouraging. One study compared the coated
balloon to a paclitaxel-eluting stent (Unverdorben et al., 2009), and found late loss at 12
months to be significantly lower for the balloon compared to the stent. Adverse events
were also significantly fewer in the DEB cohort. Paclitaxel appears to be the drug of choice
in these DEBs, primarily because of the long retention time in tissue of paclitaxel after
administration (Mori et al., 2006).
The predominant use of DEBs is for treatment of ISR, as double-stenting in the same
area is not advisable. ISR rates (as mentioned before) for DES are about 8-10%, and DEBs
have taken over this segment of the market. With improved methods of delivery and more
clinical data, it is likely that DEBs will continue to make further inroads into the DES
segment.
Other Bioactive-Eluting Implants: Orthopedic Applications
As mentioned in the “Introduction,” there are very few coated implants, other than stents,
that release bioactive compounds in vivo. The field of bioactive coatings for osteo implants
(Figure 10.4) has been covered well in a 2008 review (Pioletti et al., 2008).
Of the various options, the first is a coating of a carrier film containing the bioactive
molecule, and this carrier film may be a calcium phosphate or a polymer. The second and
third options involve incorporation of drug into the body of the implant and will not con-
cern us here.
Of the bioactives that have been studied, the most clinically relevant ones appear
to be bisphosphonates, or BP and bone morphogenic protein, or BMP. BP are excellent
molecules for inhibition of osteoclasts and thus help in minimizing bone resorption.
Clinically, their administration is done primarily to prevent or minimize bone loss in
osteoporosis, Paget's disease, bone lytic tumors, and periodontal disease. However, their
use in coated osteoimplants is being increasingly recognized.
BPs target the catabolic phase of bone remodeling, where the osteoclasts are active in
removing callus. BMP is involved in the anabolic phase, where tissue regeneration occurs.
However, the required physiological dose of BMP required to inhibit osteoclasts is high
and so is the cost. Therefore, BPs appear to be the agent of choice in osteoimplants.
