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.