Pegylated liposomes have potential as vehicles for intratumoral and subcutaneous drug delivery.
Pegylated liposomes have potential as vehicles for intratumoral and subcutaneous drug delivery.
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发表时间：
2000-06
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通讯作者：
K. J. Harrington;K. J. Harrington;G. Rowlinson‐Busza;Konstantinos N. Syrigos;P. Uster;Richard Vile;J. Stewart
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作者：
K. J. Harrington;K. J. Harrington;G. Rowlinson‐Busza;Konstantinos N. Syrigos;P. Uster;Richard Vile;J. Stewart
肿瘤内或s.c.作为正在进行的旨在开发用于治疗头颈癌的聚乙二醇化脂质体放射增敏剂的计划的一部分，在裸鼠中评估了注射聚乙二醇化脂质体作为肿瘤及其引流淋巴结的局部区域靶向治疗。动物接受（111）In标记的二亚乙基三胺五乙酸（DTPA），包封在聚乙二醇化脂质体（IDLPL）中或以未包封形式（（111）In-DTPA），作为瘤内或s.c.注射，并测量局部保留、局部区域淋巴结引流和全身生物分布。在肿瘤内注射后，IDLPL有效地保留在肿瘤中，在1和96小时之间的曲线下面积（AUC）为2，574.4%注射剂量/克小时（%ID/g x h）。（111）In-DTPA的相应值为204.4%ID/g × h。在同侧淋巴结中观察到IDLPL蓄积。24 h时腹股沟淋巴结的最大同侧：对侧淋巴结比为8：1（2.2 vs 0.27%ID/g），48 h时腋窝淋巴结的最大同侧：对侧淋巴结比为19：1（2.5 vs 0.13%ID/g）。未包封的（111）In-DTPA在局部淋巴结中未显示蓄积证据。皮下注射后注射后，IDLPL从注射部位缓慢清除，1至192 h之间的AUC为24，051.1%ID/g x h。未包封的（111）In-DTPA被迅速清除，1 - 192 h的AUC为46.4%ID/g x h。同样，在同侧局部区域淋巴结中检测到显著水平的IDLPL，24 h时（腹股沟淋巴结）同侧：对侧比率为121：1（57.9 vs 0.48%ID/g），72 h时（腋窝淋巴结）为17：1（5.2 vs 0.3%ID/g）。未包封的（111）In-DTPA在引流结中无滞留。聚乙二醇化脂质体放射增敏剂的局部给药可能是头颈部肿瘤及其淋巴结转移的靶向治疗的一种有用方法。
The potential value of intratumoral or s.c. injections of pegylated liposomes as locoregionally targeted therapy of tumors and their draining lymph nodes was assessed in nude mice as part of an ongoing program aimed at developing pegylated liposomal radiosensitizers for the treatment of head and neck cancers. Animals received (111)In-labeled diethylenetriaminepentaacetic acid (DTPA), either encapsulated in pegylated liposomes (IDLPL) or in the unencapsulated form ((111)In-DTPA), as intratumoral or s.c. injections, and the local retention, locoregional nodal drainage, and systemic biodistribution were measured. After intratumoral injections, IDLPL were effectively retained in the tumor with an area under the curve (AUC) between 1 and 96 h of 2,574.4% injected dose per gram hours (%ID/g x h). The corresponding value for (111)In-DTPA was 204.4%ID/g x h. Accumulation of IDLPL was seen in ipsilateral lymph nodes. The maximal ipsilateral:contralateral node ratios were 8:1 (2.2 versus 0.27%ID/g) for inguinal nodes at 24 h and 19:1 (2.5 versus 0.13%ID/g) for axillary nodes at 48 h. Unencapsulated (111)In-DTPA showed no evidence of accumulation in locoregional nodes. After s.c. injection, IDLPL were cleared slowly from the injection site with an AUC between 1 and 192 h of 24,051.1%ID/g x h. Unencapsulated (111)In-DTPA was cleared rapidly with an AUC between 1 and 192 h of 46.4%ID/g x h. Again, significant levels of IDLPL were detected in the ipsilateral locoregional nodes, with ipsilateral:contralateral ratios of 121:1 (57.9 versus 0.48%ID/g) at 24 h (inguinal nodes) and 17:1 (5.2 versus 0.3%ID/g) at 72 h (axillary nodes). There was no retention of unencapsulated (111)In-DTPA in the draining nodes. Locoregional administration of pegylated liposomal radiosensitizers may be a useful approach for targeted therapy of head and neck tumors and their nodal metastases.