Aurora kinase as the RQ1 loading of RESV and QUER are both associated with similar burst and sustained kinetics. A limitation of our approach may be that arterial transport was assumed to be solely diffusion mediated. Although the importance of convection, or pressure driven drug transport, with regard to stent based drug delivery has not been conclusively demonstrated,48 this phenomenon may also play a role in arterial drug movement.21 As noted in the simulation, the nature of the convective drug loss from the artery due to blood flow was substituted with a constant zero concentration at the luminal surface. This boundary condition simplifies the complex molecular interactions that describe drug transport from the arterial wall into the blood compartment. Future studies are needed to fully characterize the relationship between diffusive and convective mechanisms in mediating RESV and QUER transport within the arterial wall. CONCLUSIONS Using a computational model, we were able to jak stat predict how initial polymer drug loading affects drug release profile and how release kinetics influence arterial levels of two vascular protective polyphenols, RESV and QUER.
Although predicted arterial drug content showed some TCR pathway dependence on polymer release kinetics, differences in physicochemical drug properties were shown to have a dramatic effect on tissue drug level. Disparity between predicted arterial levels of RESV and QUER are likely due to differences in protein binding, leading to greater tissue partitioning and the maintenance of higher levels of RESV over 28 days. Within the context of device safety, it is critical to consider the local pharmacokinetics of stent based therapeutics, especially when delivering drugs with narrow therapeutic margins such as Taxol. This study reiterates that drug polarity and protein binding are important factors that not only influence release profile from a polymer film but also determine the concentration profile within arterial tissue. ACKNOWLEDGMENTS This work was supported by the Edward P. Stiles Intramural Research Award. We thank Dr. Derrick K. Rollins of Iowa State University for advice on the statistics used for external validation of the proposed computational model. James J. Kleinedler, John D. Foley, and Tammy R. Dugas are inventors on patent PCT/US2008/082440 titled Coated devices and methods of making coated anastrozole devices that reduce smooth muscle cell proliferation and platelet activation.
John D. Foley and Tammy R. Dugas are cofounders of ReQuisite Biomedical, a company commercializing medical device coatings. Entomopathogenic nematodes are biological control agents that are pathogenic to a wide variety of insect pests. Bacteria of the genera Xenorhabdus and Photorhabdus are known to be symbiotically associated with the soil dwelling EPN of the family steinernematidae and heterorhabditidae, respectively. The bacteria are carried by the infective juveniles of the transport nematode, which infect the insect host by penetrating through natural openings viz. mouth, anus or spiracles. The bacteria are released by the nematode into the insect body cavity, and both the nematode and the bacteria kill the host rapidly within 48 h. The insect cadaver does not putrefy, apparently due to the production of antimicrobial compounds.