Biodistribution and clearance of intra-articular Liposomes in a large animal model using a radiographic marker
Biodistribution and clearance of intra-articular Liposomes in a large animal model using a radiographic marker
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DOI：
10.1080/08982100701557129
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Read, Richard A.
中科院分区：
文献类型：
--
作者：
Edwards, Scott H. R.;Cake, Martin A.;Read, Richard A.
治疗关节炎的关节内（IA）给药途径具有将药物靶向递送至受影响组织的潜力，从而使全身给药药物的伴随副作用最小化。然而，滑膜的超微结构有助于药物从关节快速流出;在吸收和重新分布到体循环方面，IA途径与其他非IV胃肠外途径有效等同。本研究的目的是通过使用脂质体制剂延长药物在膝关节内的停留时间。以放射性造影剂碘海醇为药物标记物制备DPPC脂质体。8只绵羊的右膝关节内注射碘海醇脂质体，对侧关节内注射游离碘海醇或空脂质体。在注射后16天内的多个时间点对关节进行X射线照相。碘海醇介导的不透射线性通过光密度计定量。研究结束时处死绵羊，进行滑膜组织显微镜检查。在整个实验过程中，碘海醇介导的不透射线性具有良好的可视化和精细的解剖学定义。在胶片上也明显可见关节外不透射线性，脂质体沿沿着肌肉面平面追踪。通过使用冷冻切片和大的脂质体尺寸，可以用光学显微镜进行细胞和组织定位。胶囊化碘海醇在膝关节内的驻留时间大大延长。碘海醇脂质体呈双指数下降，终末消除半衰期为134小时。相比之下，注射后3小时未检测到游离碘海醇。
The intra-articular (IA) route of administration in treating arthritis has potential for targeting drug delivery to affected tissues, thereby minimising the attendant side-effects of systemically administered drugs. The ultra-structure of the synovium however facilitates rapid drug efflux from the joint; effectively the IA route is equivalent to other non-IV parenteral routes with regards absorption and redistribution into the systemic circulation. The aim of this study was to extend the drug residence time within the knee joint by using a liposome formulation. DPPC-based liposomes were prepared with the radio contrast agent iohexol as a drug marker. 8 sheep had their right knees injected IA with iohexol liposomes and the contralateral joints with either free iohexol or empty liposomes. Joints were radiographed at multiple time points up to 16 days post-injection. Iohexol-mediated radiopacity was quantified by densitometer. Sheep were sacrificed at the end of the study for microscopy of synovial tissues. Good visualization of iohexol-mediated radiopacity with fine anatomical definition was possible throughout the experiment. Also evident on the films was extra-articular radiopacity with liposomes tracking along muscle facial planes. Cellular and tissue localization with light microscopy was possible through use of frozen sections and because of the large liposome size. Residence of encapsulated iohexol within the knee joint was greatly prolonged. Liposomal iohexol declined bi-exponentially with a terminal elimination half-life of 134 hours. In contrast, free iohexol was undetectable @ 3 hours post-injection.