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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: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。
Objective: To investigate the distribution and metabolism of vincristine-loaded red blood cells in mice. Methods: Kunming mice were subcutaneously inoculated with S180 sarcoma into the armpit of mice to establish a tumor-bearing mouse model. The tumor-bearing mice were randomly divided into two groups: vincristine and vincristine-loaded erythrocytes. 200 ug of vincristine was injected through tail vein, Vincristine drug-loaded red blood cells (concentration 1cg / L). At 0, 1, 2, 3, 4, 24, 48 and 72 hours after injection, the blood, liver and tumor tissues were taken from the mice. The drug concentration was measured by HPLC and the half-life was calculated. Results: The vincristine rapidly increased plasma concentration after entering the body, its metabolic rate is also very fast, completely undetectable after 48h, half-life of 1.53h. Vincristine drug-loaded erythrocytes in plasma concentration stable and durable, 72h can still be measured, the drug half-life of 4.1h, 2.68 times the former. The concentration and stability of drug-loaded erythrocytes in liver and tumor were higher than those of free drug, and the advantage was more and more obvious with the extension of time. Conclusion: Drug-loaded erythrocytes delay drug release and prolong drug action time. Drug-targeted erythrocytes enhance target-specific aggregation to liver and tumor and reduce adverse reactions. Provide new ideas and feasible methods for clinical oncology treatment.