Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Pharm Res. 2013 Oct;30(10):2654-63. doi: 10.1007/s11095-013-1091-7. Epub 2013 Jun 6.
This article describes the preparation, physicochemical characterization and in vivo assessment of parenteral colloidal formulation of flutamide (FLT) based on biocompatible casein (CAS) self-assembled micelles in order to control drug release, enhance its antitumor efficacy and reduce its hepatotoxicity.
Spray-drying technique was successfully utilized to obtain solidified redispersible drug-loaded micelles.
Spherical core-shell micelles were obtained with a particle size below 100 nm and a negative zeta potential above -30 mV exhibiting a sustained drug release up to 5 days. After intravenous administration into prostate cancer bearing rats for 28 days, FLT-loaded CAS micelles showed a higher antitumor efficacy as revealed by significantly higher reduction in PSA serum level (65.95%) compared to free FLT (55.43%). Moreover, micellar FLT demonstrated a marked decrease in relative weights of both prostate tumor and seminal vesicle (34.62 and 24.59%) compared to free FLT (11.86 and 17.74%), respectively. These antitumor responses were associated with notable reduction of cell proliferation, intratumoral angiogenesis and marked increase of tumor apoptosis. A significantly lower risk of hepatotoxicity was observed by micellar FLT as evidenced by lower alanine aminotransferase (ALT) serum level compared to free FLT.
Overall this approach suggested that CAS micelles might be an ideal candidate for intravenous delivery of hydrophobic anticancer drugs.
本文描述了基于生物相容的酪蛋白（CAS）自组装胶束的非那雄胺（FLT）的胶体制剂的制备、理化特性和体内评估，以控制药物释放、增强其抗肿瘤疗效并降低其肝毒性。
成功利用喷雾干燥技术获得了固体分散的载药胶束。
得到了粒径低于 100nm、zeta 电位低于-30mV 的球形核壳胶束，表现出长达 5 天的持续药物释放。在荷前列腺癌大鼠静脉注射 28 天后，载药 CAS 胶束显示出更高的抗肿瘤疗效，表现为 PSA 血清水平显著降低（65.95%），而游离 FLT 为（55.43%）。此外，与游离 FLT 相比，载药胶束的前列腺肿瘤和精囊的相对重量分别显著降低（34.62%和 24.59%）。这些抗肿瘤反应与细胞增殖、肿瘤内血管生成的显著减少和肿瘤凋亡的显著增加有关。载药胶束的肝毒性风险明显降低，表现为丙氨酸氨基转移酶（ALT）血清水平低于游离 FLT。
总之，该方法表明 CAS 胶束可能是静脉内递运疏水性抗癌药物的理想候选物。
