Choi Yongdoo, Kim Sang Yoon, Kim Sun Hee, Yang Jehoon, Park Kyeongsoon, Byun Youngro
Department of Material Science and Engineering, Kwangju Institute of Science and Technology, Gwangju, Korea.
Int J Cancer. 2003 Oct 20;107(1):145-8. doi: 10.1002/ijc.11354.
Retinoids play essential roles in the regulation of cell differentiation and in the proliferation of various epithelial tissues, and atRA is one such active metabolite of retinoids. However, despite the known functions of atRA, its clinical applications are limited due to the induced metabolism by the specific cytochrome P-450s in the liver. To overcome the limitation, parenteral administration of atRA-loaded biodegradable microspheres, the PDLLA/PLE microspheres containing atRA, was suggested previously. We evaluated chemotherapeutic efficacy of atRA-loaded microspheres in a human head-and-neck xenograft/nude mouse model. When atRA-loaded microspheres were administered s.c. at 200 mg/kg body weight to athymic nude mice, plasma concentration of atRA could be maintained in a range of 1.2 to 3.7 x 10(-8) M for 4 weeks. As a result, the tumor volume of human head-and-neck cancer was reduced compared to the control group by 51.3% (p < 0.01) at 14 days and by 49.2% (p < 0.05) at 28 days.
维甲酸在细胞分化调节和各种上皮组织的增殖中发挥着重要作用，全反式维甲酸（atRA）就是维甲酸的一种活性代谢产物。然而，尽管atRA的功能已知，但其临床应用因肝脏中特定细胞色素P-450诱导的代谢作用而受到限制。为克服这一限制，先前有人提出通过肠胃外给药含atRA的可生物降解微球，即含atRA的聚乳酸-乙醇酸共聚物/聚左旋赖氨酸（PDLLA/PLE）微球。我们在人头颈异种移植/裸鼠模型中评估了含atRA微球的化疗效果。当以200mg/kg体重的剂量将含atRA微球皮下注射给无胸腺裸鼠时，atRA的血浆浓度可在1.2至3.7×10⁻⁸M范围内维持4周。结果，与对照组相比，人头颈癌的肿瘤体积在第14天时减少了51.3%（p<0.01），在第28天时减少了49.2%（p<0.05）。
