Comparison of doxorubicin concentration profiles in radiofrequency-ablated rat livers from sustained- and dual-release PLGA millirods.

Abstract

To evaluate and compare the local pharmacokinetics of doxorubicin in radiofrequency (rf)-ablated rat livers after interstitial delivery from sustained- and dual-release poly(D,L-lactide-co-glycolide) (PLGA) millirods. PLGA millirods with sustained- and dual-release kinetics (burst followed by sustained release) of doxorubicin were implanted in rf-ablated rat livers. Doxorubicin release kinetics in vivo were measured from explanted millirods by UV-Vis spectrophotometer over 8 days. Spatial distribution of doxorubicin in liver tissues was measured by fluorescence imaging. In the initial 24 h after millirod implantation, dual-release millirods released significantly more doxorubicin into liver tissues than the sustained millirods. Subsequently, both types of millirods provided comparable sustained-release kinetics over 8 days. With dual-release millirods, doxorubicin concentration and penetration distance in liver tissue increased more rapidly. To reach 30 microg/g doxorubicin concentration at the ablation boundary (targeted site of action), the time required was 6 days and 1.5 days for sustained- and dual-release millirods, respectively. Compared with sustained-release millirods, dual-release millirods provide a quick concentration elevation and sustaining of the drug concentration at the ablation boundary. Additionally, the steady-state drug concentration agrees well with model predictions based on previously determined transport parameters, which demonstrates the feasibility of rational design of drug formulations in polymer millirods.