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Depth Profiling of Drug Eluting Stent Coatings with Cluster SIMS

Summary:

There is much excitement in the cardiology community about drug eluting stents (DES), a promising new treatment for coronary artery disease. A coronary stent is a small coiled wire-mesh tube that is inserted into a blood vessel and expanded using a small balloon during an angioplasty procedure. When the balloon is inflated, the stent expands, locks in place and forms a scaffold to hold the artery open, improving blood flow to the heart muscle and decreasing the probability of restenosis or renarrowing of the artery. These stents often incorporate a drug delivery system consisting of a polymeric layer or coating containing a drug, where the drug acts to further prevent the build up of smooth muscle cells on the stent. It is particularly important in DES to characterize the molecular composition of the surface and near surface region of the device (1-500 nm) because this region controls the biocompatibility and influences the magnitude and temporal variation of drug release. Secondary Ion Mass Spectrometry (SIMS) has already proven to be a useful tool in the surface analysis of various drug delivery systems. With SIMS, the molecular distribution of both drugs and excipients within a drug delivery systems can be determined with a high degree of spatial resolution (<1µm) and sensitivity (as low as ppm (µg/g)) when compared to other analytical methods such as Raman and IR spectroscopies. Furthermore, with the advent of polyatomic primary ion sources (C60+, Bi3+ and SF5+), which yield significant improvements in molecular signals (up to 1000 fold increase), and result in decreased beam-induced damage accumulation, it is now possible to obtain 3-dimensional compositional information from model systems, particularly at low temperatures which yield optimum results.

Description:

Secondary Ion Mass Spectrometry (SIMS) employing an SF5+ polyatomic primary ion source for sputtering and Bi3+ primary ions for analysis was used to depth profile through DES coatings obtained from Medtronic (DES manufacturer) at variable temperatures. PLGA/Rapamycin films were prepared by casting solutions of 2% w/v poly(lactic-co-glycolic acid) (PLGA) containing 5% w/w rapamycin (~6 µm) onto steel substrates, and a SIMS depth profile was acquired at room temperature. The signal was observed to decay at SF5+ primary ion doses of ~1.3 x 10^15 SF5+ ions/cm2 and the steel substrate was never reached. However, the depth profile stability was dramatically improved at low temperatures (-100 degrees C), as indicated by the relatively constant signal up through SF5+ primary ion doses of ~1.5 x 10^16 SF5+ ions/cm2. At this dose the secondary ions characteristic of the DES coating decreased while the corresponding steel substrate intensities increased, indicating that the entire film was eroded. This result shows that using low temperatures can extend the utility of SF5+ to characterize thicker polymeric materials (6.0 µm as opposed to 0.2 µm).

Cluster SIMS at low temperatures has also be used to elucidate the 3-dimensional structure in these DES coatings, as illustrated in the Figure, which shows secondary ion image overlays of m/z = 99 (fragment characteristic of PLGA) and m/z = 84 (fragment characteristic of Rapamycin) in a PLGA film containing 25% rapamycin. These images were acquired as a function of increasing sputter time or depth, and thus give detailed information on the heterogeneity in the surface and near surface region in these systems as compared to the bulk. To our knowledge, these images represent the first demonstration of successful 3-D SIMS imaging in real world drug delivery devices.

Overlay of SIMS images acquired as function of increasing SF5+ sputter time in a PLGA film containing 25% Rapamycin

Start Date:

February 14, 2007

End Date:

ongoing

Lead Organizational Unit:

mml

Customers/Contributors/Collaborators:

Anna Belu
Medtronic Inc
Minneapolis, MN

Contact

Specific Information:
Christine Mahoney
301-975-8515 Telephone
christine.mahoney@nist.gov

100 Bureau Drive, M/S 8371
Gaithersburg, MD 20899-8371