(293e) Sterilization of Anti-Microbial Surface Coatings

                Device-related
infections at a medical implant site cause catastrophic complications for the
patient. Various local drug delivery devices and coatings are being developed
as slow, sustained release mechanisms at the implantation site to prevent
device-related infections. One example of a promising drug delivery system is a
cyclodextrin polymer which has effective in vitro and in vivo
release over 45 days.^1,2 In
this study, we show that the effective release can be extended beyond 8 months
of delivery. One lingering concern regarding these materials is the effect of
sterilization, which is critical for use as implantable biomedical devices or
device coatings. Herein, we examine the effect that commercial sterilization techniques
have on the physical, mechanical, and drug delivery properties of these
materials; however, the work can be extended to other similar materials or
applications.

                Specifically,
we will report on cyclodextrin polymers which have been subjected to autoclave,
ethylene oxide, or gamma radiation and then loaded with antibiotics. Thermomechanical
tests, including thermogravimetric analysis, differential scanning calorimetry,
and tensile tests, will be presented. We will also evaluate how sterilization
impacts the drug loading, release rate, and anti-microbial activity of three
different antibiotics:  vancomycin,
rifampicin, and erythromycin. (Erythromycin was previously untested with these
materials). Validating that these materials can be sterilized, and still prove
effective in their anti-microbial function, is critical prior to clinical use.

                We
found that there is no significant change in the release rate or the total amount
of drug released from ethylene oxide and gamma radiation sterilized polymers.
In autoclave sterilized polymers, a reduction in the amount of total drug loaded
and released was observed, yet the autoclaved polymers also showed a longer
sustained release. These two changes amount to interesting implications in
using additional thermo-processing, such as the autoclave, to modify rate and
dose from these materials.  We suspect
that the change in the release profile was caused by additional crosslinking from
residual, unreacted, or partially-reacted crosslinker contained within the
polymer, although confirming this chemical change is the aim of future
research.

1.            Thatiparti
TR, von Recum HA. Cyclodextrin complexation for affinity-based antibiotic
delivery. Macromolecular Bioscience 2010;10:82-90.

2.            Thatiparti
TR, Shoffstall AJ, von Recum HA. Cyclodextrin-based device coatings for
affinity-based release of antibiotics. Biomaterials 2010;31:2335-2347.