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 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.
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 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.
Authors: G D Dodd; M C Soulen; R A Kane; T Livraghi; W R Lees; Y Yamashita; A R Gillams; O I Karahan; H Rhim Journal: Radiographics Date: 2000 Jan-Feb Impact factor: 5.333
Authors: M C Alley; D A Scudiero; A Monks; M L Hursey; M J Czerwinski; D L Fine; B J Abbott; J G Mayo; R H Shoemaker; M R Boyd Journal: Cancer Res Date: 1988-02-01 Impact factor: 12.701
Authors: Brent D Weinberg; Ravi B Patel; Hanping Wu; Elvin Blanco; Carlton C Barnett; Agata A Exner; Gerald M Saidel; Jinming Gao Journal: Med Biol Eng Comput Date: 2008-06-04 Impact factor: 2.602