A novel method for efficient drug delivery.
Local delivery of anti-thrombotic and anti-restenotic drugs is desired to achieve high concentrations of agents which may be rapidly degraded systemically or which exhibit very short half-lives in vivo. In this article, the operating characteristics of a novel local drug delivery method are described and its effectiveness demonstrated computationally and experimentally. Computational models used a finite volume method to determine the concentration field. Optical dye density measurements of Evans blue in saline were performed in an in vitro steady flow system. Modeling parameters were kept in the physiologic range. Experimental flow visualization studies demonstrated high concentrations of infusate near the vessel wall. Computational studies predicted high, clinically significant drug concentrations along the wall downstream of the infusion device. When the radial infusion velocity is large (infusion flow rate, Qinf>0.5% of the main flow rate, Q), the wall concentration of the infused drug remains high, e.g., levels are greater than 80% of the infusate concentration 5 cm downstream of the infusion device. At lower infusion rates (Qinf<0.001Q), the drug concentration at the wall decreases exponentially with axial distance to less than 25% of the infusate concentration 5 cm downstream of the infusion device, although therapeutic drug levels are still readily maintained. The near wall drug concentration is a function of flow conditions, infusion rate, and the drug diffusivity. Good agreement was obtained between computational and experimental concentration measurements. Flow simulation and experimental results indicate that the technique can effectively sustain high local drug concentrations for inhibition of thrombosis and vascular lesion formation.
Markou
C P
CP
Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Lutostansky
E M
EM
Ku
D N
DN
Hanson
S R
SR
D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000188:drug therapy; D019295:Computational Biology; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000379:methods*; D007262:Infusions, Intravenous / Q000379:methods; D008954:Models, Biological; D013927:Thrombosis / Q000188:drug therapy
D000991:Antithrombins