Inhibition of tumor growth by biodegradable microspheres containing all-trans-retinoic acid in a human head-and-neck cancer xenograft.

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.