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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Qian
Feng
F
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Stowe
Nicholas
N
Saidel
Gerald M
GM
Gao
Jinming
J
D000818:Animals; D017115:Catheter Ablation; D004317:Doxorubicin / Q000493:pharmacokinetics; D007700:Kinetics; D008099:Liver; D011108:Polymers; D051381:Rats
D011108:Polymers; D004317:Doxorubicin