Characterization of a novel intrinsically radiopaque Drug-eluting Bead for image-guided therapy: DC Bead LUMI™.
Characterization of a novel intrinsically radiopaque Drug-eluting Bead for image-guided therapy: DC Bead LUMI™.
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DOI：
10.1016/j.jconrel.2017.02.001
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发表时间：
2017-03-28
期刊：
影响因子：
--
通讯作者：
Lewis AL
中科院分区：
文献类型：
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作者：
Ashrafi K;Tang Y;Britton H;Domenge O;Blino D;Bushby AJ;Shuturminska K;den Hartog M;Radaelli A;Negussie AH;Mikhail AS;Woods DL;Krishnasamy V;Levy EB;Wood BJ;Willis SL;Dreher MR;Lewis AL
我们开发了一种直接而有效的方法，将不透射线引入到目前临床用于治疗肝脏恶性肿瘤的聚乙烯醇-2-丙烯酰胺-2-甲基丙磺酸(AMPS)水凝胶微珠(DC-™)中。将2，3，5-三碘苯甲醛偶联到预成型微珠的PVA主链上，可产生附着在整个微珠结构中的均匀分布的碘水平(~150毫克/毫升)，足以在治疗程序(DC微珠流明™)中使用的标准透视和计算机断层扫描(CT)成像方式下进行成像。尽管进行了化学修饰，使微珠的密度增加到~1.3g/cm3，压缩模数增加了两个数量级，但它们仍然很容易悬浮，通过标准的微导管进行操作和给药。由于DC微珠LUMI™的核心化学与DC微珠™相同，它通过聚合物上的磺酸基团与药物中带正电的胺基之间的离子交换与药物相互作用。阿霉素(DOX)和伊立替康(IRI)的洗脱动力学均在DC珠™的临床研究参数范围内。载药量不影响放射不透度，微珠衰减与药物浓度有直接关系。通过在荧光透视下将负载™的DC微珠注入兔肝动脉，随后进行CT成像，证实了负载DOX的DC微珠LUMI在体内可见的能力。
We have developed a straightforward and efficient method of introducing radiopacity into Polyvinyl alcohol (PVA)-2-Acrylamido-2-methylpropane sulfonic acid (AMPS) hydrogel beads (DC Bead™) that are currently used in the clinic to treat liver malignancies. Coupling of 2,3,5-triiodobenzaldehyde to the PVA backbone of pre-formed beads yields a uniformly distributed level of iodine attached throughout the bead structure (~150 mg/mL) which is sufficient to be imaged under standard fluoroscopy and computed tomography (CT) imaging modalities used in treatment procedures (DC Bead LUMI™. Despite the chemical modification increasing the density of the beads to ~1.3 g/cm3 and the compressive modulus by two orders of magnitude, they remain easily suspended, handled and administered through standard microcatheters. As the core chemistry of DC Bead LUMI™ is the same as DC Bead™, it interacts with drugs using ion-exchange between sulfonic acid groups on the polymer and the positively charged amine groups of the drugs. Both doxorubicin (Dox) and irinotecan (Iri) elution kinetics for all bead sizes evaluated were within the parameters already investigated within the clinic for DC Bead™. Drug loading did not affect the radiopacity and there was a direct relationship between bead attenuation and Dox concentration. The ability (Dox)-loaded DC Bead LUMI™ to be visualized in vivo was demonstrated by the administration of into hepatic arteries of a VX2 tumor-bearing rabbit under fluoroscopy, followed by subsequent CT imaging.