Szymanski-Exner A, Gallacher A, Stowe N T, Weinberg B, Haaga J R, Gao J
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio, USA.
J Biomed Mater Res A. 2003 Nov 1;67(2):510-6. doi: 10.1002/jbm.a.10038.
This study investigated the local drug pharmacokinetics of intralesional drug delivery after radiofrequency ablation of the liver. We hypothesized that the tissue architecture damaged by the ablation process facilitates the drug penetration in the liver and potentially enlarges the therapeutic margin in the local treatment of cancer. The delivery rate and tissue distribution of carboplatin, an anticancer agent, released from poly(D,L-lactide-co-glycolide) implants into rat livers after radiofrequency ablation were quantified by atomic absorption spectroscopy. Results showed that carboplatin clearance through blood perfusion was significantly slower in the ablated livers, leading to a more extensive tissue retention and distribution of the drug. The concentration of Pt at the implant-tissue interface ranged from 234 to 1440 microg Pt/(g liver) in the ablated livers over 144 h versus 56 to 177 microg Pt/(g liver) in the normal tissue. The maximum penetration distance at which Pt level reached above 6 microg/g (calculated based on a reported IC90 value for carboplatin) was 8-10 mm and 4-6 mm in ablated and normal liver, respectively. Histological analysis of the necrotic lesions showed widespread destruction of tissue structure and vasculature, supporting the initial hypothesis. This study demonstrated that intralesional drug delivery could provide a sustained, elevated concentration of anticancer drug at the ablation boundary that has the potential to eliminate residual cancer cells surviving radiofrequency ablation.
本研究调查了肝脏射频消融术后瘤内给药的局部药物药代动力学。我们假设，消融过程造成的组织结构破坏有助于药物在肝脏中的渗透，并可能扩大癌症局部治疗的治疗边界。通过原子吸收光谱法定量测定了聚（D，L-丙交酯-共-乙交酯）植入物释放的抗癌药物卡铂在大鼠肝脏射频消融后的递送速率和组织分布。结果表明，消融肝脏中通过血液灌注的卡铂清除率明显较慢，导致药物在组织中的滞留和分布更为广泛。在144小时内，消融肝脏中植入物-组织界面处的铂浓度范围为234至1440微克铂/（克肝脏），而正常组织中为56至177微克铂/（克肝脏）。铂水平达到6微克/克以上（根据报道的卡铂IC90值计算）的最大穿透距离在消融肝脏中为8-10毫米，在正常肝脏中为4-6毫米。坏死病变的组织学分析显示组织结构和脉管系统广泛破坏，支持最初的假设。本研究表明，瘤内给药可在消融边界提供持续升高的抗癌药物浓度，有可能消除射频消融后存活的残留癌细胞。
