TY - JOUR
T1 - Comparison of doxorubicin concentration profiles in radiofrequency-ablated rat livers from sustained- and dual-release plga millirods
AU - Qian, Feng
AU - Stowe, Nicholas
AU - Saidel, Gerald M.
AU - Gao, Jinming
N1 - Funding Information:
This work was supported by the National Institutes of Health (R01-CA-90696).
PY - 2004/3
Y1 - 2004/3
N2 - Purpose. 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 μg/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.
AB - Purpose. 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 μg/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.
KW - Doxorubicin
KW - Dual-release kinetics
KW - Intratumoral drug delivery
KW - Poly(D,L-lactide-co-glycolide)
KW - Radiofrequency ablation
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U2 - 10.1023/B:PHAM.0000019290.70358.30
DO - 10.1023/B:PHAM.0000019290.70358.30
M3 - Article
C2 - 15070087
AN - SCOPUS:1542406601
SN - 0724-8741
VL - 21
SP - 394
EP - 399
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 3
ER -