Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Pharm Res. 2004 Mar;21(3):394-9. doi: 10.1023/B:PHAM.0000019290.70358.30.
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.
评估和比较射频（rf）消融大鼠肝脏中多柔比星（doxorubicin）在间质给药后，来自持续和双重释放聚（D，L-丙交酯-共-乙交酯）（PLGA）毫微棒的局部药代动力学。
将具有持续和双重释放动力学（爆发后持续释放）的多柔比星的 PLGA 毫微棒植入射频消融的大鼠肝脏中。通过紫外可见分光光度计在 8 天内从离体毫微棒中测量体内多柔比星释放动力学。通过荧光成像测量肝组织中多柔比星的空间分布。
在毫微棒植入后的最初 24 小时内，双重释放毫微棒向肝组织中释放的多柔比星明显多于持续释放毫微棒。随后，两种类型的毫微棒在 8 天内提供了可比的持续释放动力学。使用双重释放毫微棒，肝组织中的多柔比星浓度和穿透距离增加得更快。为了在消融边界（作用靶点）处达到 30μg/g 的多柔比星浓度，持续和双重释放毫微棒所需的时间分别为 6 天和 1.5 天。
与持续释放毫微棒相比，双重释放毫微棒在消融边界处提供了药物浓度的快速升高和维持。此外，稳态药物浓度与基于先前确定的转运参数的模型预测吻合良好，这证明了在聚合物毫微棒中合理设计药物配方的可行性。
