E. Wuyts 1,2, J.Sohier 2, B. Op de Beeck3, B. Camps 2, B. Sels,3 G. Van Den Mooter 1
Laboratory for Pharmacotechnology and Biopharmacy; University of Leuven; Campus
Gasthuisberg, O&NII; Herestraat 49 b 921; 3000 Leuven
Ziscoat nv.; Researchpark Haasrode 1820; Interleuvenlaan 62; 3001 Heverlee
Center for Surface Chemistry and Catalysis, Kasteelpark Arenberg 23 b 2461,3001 Heverlee
Cardiovascular diseases (e.g arthrosclerosis) are the primary cause of death in our Western
Society. A possible treatment for arthrosclerosis is the implantation of a drug eluting stent (DES).
Its advantage in comparison with bare stents is that the addition of drugs can prevent restenosis.
The goal of this research project is to develop a coating that is biocompatible, bioabsorbable,
plastically deformable and has a controllable drug release.
The developed coatings are based on 3 or more triacylglycerols, which undergo an
interesterification reaction to interexchange the acyl residues. The interesterification reaction is
executed by weighing the triaglycerols, followed by drying them overnight in a vacuum oven at
100°C. Next, sodiummethoxide is added. The reaction completes within 1 hour under a nitrogen
flow. To stop the reaction, 2 ml of a 20 wt% citric acid solution is added and the reaction
compartment is cooled down. Afterwards the mixture is washed several times and dried at 100°C.
The last step is to filter the mixture through a membrane filter in a vacuum oven at 100°C.1 To
control the distribution of the randomized triacylglycerols, the coatings are analyzed with HPLC
RI. The coatings are further characterized by their slip melting point (SMP)2
After interesterification, the coating material is checked for mechanical and drug release
properties. Therefore, the coating is applied on stent samples with a home built spraying device.
For each coating composition, the spraying parameters are optimized to obtain an equal coating
distribution on the stent material.
Mechanical properties are investigated by performing integrity tests and stent crimping and
expansion tests. Coating integrity is checked with a simulated stenosis test at 37°C, in which the
applied pressure can be changed. For a low pressure, the loss of coating material is about 5 %,
while for a high pressure, the loss of coating rises up to 10 - 15%. Also, scratch tests with the
Falex MUST tester are performed, which showed a good coating resistance against scratches.
Stent crimping is performed manually. Before and after stent crimping and stent expansion, stents
are visually checked with a light microscope for defects such as cracks or delaminations.
In order to test the performance of the coatings, the in vitro release of paclitaxel and rapamycine
from coated stents was tested. The in vitro drug release is performed at 37°C and is analyzed with
HPLC UV-VIS. After an initial burst during the first 2 – 4 hours, the drug release is constant and
mediated by diffusion. After 24 h, less then 10% is released, followed by a period of constant
release for several weeks to months, depending on the coating composition.
Triglyceride based coatings are promising to control drug release from stents during several
Bayense, C., Reesink, B. and Berben, P. (1995). A process for the interesterification of triglycerides. International
Patent C11C 3/10, International publication number WO95/16014
Karabulut, I., Turan, S. and Ergin, G. (2004). Effects of chemical interesterification on solid fat content and slip
melting point of fat/oil blends. European Food Res Technology, 218: 224-229
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