长春新碱载体红细胞体内代谢分布的初步研究

目的：初步探讨长春新碱载体红细胞在小鼠体内的分布代谢情况。方法i昆明种小鼠腋窝皮下接种S180肉瘤细胞建立荷瘤小鼠模型，将荷瘤小鼠随机分为长春新碱、长春新碱载药红细胞2组，经尾静脉分别注射长春新碱200ug及长春新碱载药红细胞（浓度1cg／L）。注射后0、1、2、3、4、24、48及72h取小鼠血液、肝脏及肿瘤组织，用高效液相色谱法测定其中药物浓度，计算半衰期。结果：长春新碱进入体内后血浆浓度迅速增高，其代谢速率也很快，48h后完全测不出，半衰期1．53h。长春新碱载药红细胞在血浆中浓度稳定而持久，72h仍可测出，药物半衰期达4．1h，是前者的2．68倍。载药红细胞在肝脏及肿瘤中的浓度和稳定性均高于游离药物，且随着时间延长，这种优势越来越大。结论：载药红细胞延缓药物释放，延长药物作用时间；增强了药物向肝脏及肿瘤的靶向聚集，减少不良反应。为临床肿瘤治疗提供新思路和可行方法。

Primary research on distribution and metabolism of VCR-loaded erythrocytes in vivo

Objective：To reveal the distribution and metabolism of VCR loaded erythrocytes in mice. Method： S180-bearing mice were randomly divided into 2 groups. Equal quantity of VCR （200ug） and VCR-loaded erythrocytes were given through vein injection respectively. Blood, liver and tumor tissue samples were collected after 0, 1,2,3,4,24,48 and 72 hr, after centrifuging supernatant was collected to detect the VCR concentration in each tissue by HPLC. The biological half life of the drug was calculated. Result：The drug concentration in plasma obviously increased soon after i.v. VCR, but it decreased quickly. The T1/2 of liberation VCR was 1.53 hr. The T1/ 2 of VCR-Er was 4.1 hr, which was 2.68 times longer than use VCR only. VCR-Er enhanced drug aggregation in liver and tumor. Conclusion：Erythrocytes as VCR carrier can make drug slow-released in vivo, keep the drug concentration stay at an appropriate level and enhance the target effect of drugs to liver and tumor tissues. This study proofs that the method of VCR-loaded erythrocytes is more advantageous and effective to tumor therapy than that of giving VCR alone.