Adrenergic receptors into the arterial tissue. Arterial Diffusivity of Taxol, RESV, and QUER To quantify the rate of drug movement through arterial tissue, transmural and planar arterial diffusion coefficients were determined using fresh carotid artery segments. RESV and Taxol shared similar transmural diffusion coefficients, whereas the transmural diffusivity of QUER was 25 fold lower, indicating that QUER diffuses faster in the transmural direction compared with RESV. Diffusivity of Taxol, RESV, and QUER was 12.6 fold, 7.0 fold, and 5.1 fold faster in the planar direction compared with diffusion transmurally. The absence of tissue binding significantly accelerated diffusivity of RESV and Taxol, but not QUER, indicating that binding does not play a significant role in the movement of QUER through the vessel wall. Simulation Results: External Validation For external validation of the proposed 2D computational model, published experimental and survivin computational drug release profiles36 from a CYPHER sirolimus eluting stent were analyzed. Drug release from a 10 :m thick polymer coating37 loaded with 140 :g/cm2 sirolimus38 was assessed over 90 days. Using Eq.
Diffusion coefficients were calculated for the burst and sustained phases of the sirolimus elution profile. Coordinates from the published curves vascular disrupting agent were extracted using the Saber software program. As shown in Figure 6, both the published model and the duallayer model capture the dynamics of the experimental release profile, as shown by Pearson correlation coefficients of 0.98 or more. The accuracy of these models was assessed using the relative average absolute error parameter. Relative AAE is the average difference between the prediction and the measured value, normalized to the standard deviation of the observed values. Thus, a smaller AAE reflects a more accurate prediction. The results showed that the dual layer heterogeneous distribution assumption results in a more accurate fit compared with the published fit. Simulation Results: Effect of Discrete Drug Distribution Within the Polymer Coating on Release Profile The effect of varying equilibrium between burst and sustained drug release on normalized peptide synthesis release profile was determined using the 2D computational model. A unit measure of drug was incorporated into the polymer compartment, with the distribution between the burst and sustained phases varying between 0:10 and 10:0.
For clarity, only five of the predicted curves are shown in each panel. The results indicated that redistribution of the drug in the polymer did not change the nature of the process, but had a determinable effect on the amount of drug released over time. By plotting the experimentally measured release profiles of RESV and QUER onto the family of simulated curves, we determined which burst sustained ratio fit the experimental data. RESV parallel within the RQ1 and RQ2 coatings showed an equilibrium distribution of 3:7 and 5:5, respectively. QUER from the RQ1 and RQ2 coatings showed an equilibrium distribution of 3:7 and 8:2, respectively. A more robust burst phase was generally associated with a more shallow sustained release phase. Simulation Results: Effect of Discrete Drug Distribution Within the Polymer Coating on Arterial Kinetics By combining experimentally derived arterial diffusion.