Truter E J
Drug Delivery Systems Research Unit, School of Life Sciences, Cape Town, Republic of South Africa.
Artif Cells Blood Substit Immobil Biotechnol. 1995;23(5):579-86. doi: 10.3109/10731199509117972.
The aim of this investigation was to study the release behaviour of heat-stabilized albumin microspheres with entrapped 5-Fluorouracil (5-FU) in vitro, and determine the organ distribution in vivo, for potential application in the treatment of ovarian cancer. Additionally, blood chemistry and haematological profiles were composed after intraperitoneal administration of 5-FU-loaded albumin microspheres into adult female Wistar rats. Microspheres with entrapped 5-FU was also added to 10(4) HeLa cells, cultured in Eagles Minimum Essential Medium, and the effects of drug leakage studied. It was found that cell division of the cells was halted before one cell cycle, as demonstrated by the absence of micronuclei and double nuclei. Blood chemistry and haematology indicated mild systemic toxic effects of the drug e.g. bone marrow suppression and liver involvement, reaching a maximum by Day 12 after intraperitoneal administration of 5-FU-microspheres. A return to normal however was observed within 4 weeks. The data suggest that 5-FU-loaded albumin microspheres may be beneficial in reducing the severe side-effects of this antimetabolite, whilst still maintaining therapeutic levels to cause tumour cell death.
本研究的目的是研究包裹5-氟尿嘧啶（5-FU）的热稳定白蛋白微球在体外的释放行为，并确定其在体内的器官分布，以探讨其在卵巢癌治疗中的潜在应用。此外，在成年雌性Wistar大鼠腹腔注射载有5-FU的白蛋白微球后，检测血液生化指标和血液学指标。将包裹5-FU的微球加入到在伊格尔氏最低限度基本培养基中培养的10(4)个HeLa细胞中，研究药物泄漏的影响。结果发现，细胞分裂在一个细胞周期之前就停止了，这可通过无微核和双核来证明。血液生化和血液学指标表明该药物有轻度的全身毒性作用，如骨髓抑制和肝脏受累，在腹腔注射5-FU微球后第12天达到最大值。然而，在4周内观察到恢复正常。数据表明，载有5-FU的白蛋白微球可能有助于减轻这种抗代谢物的严重副作用，同时仍保持治疗水平以导致肿瘤细胞死亡。
