Fenofibrate subcellular distribution as a rationale for the intracranial delivery through biodegradable carrier.

Fenofibrate subcellular distribution as a rationale for the intracranial delivery through biodegradable carrier. J Physiol Pharmacol. 2015 Apr;66(2):233-47 Authors: Grabacka M, Waligorski P, Zapata A, Blake DA, Wyczechowska D, Wilk A, Rutkowska M, Vashistha H, Ayyala R, Ponnusamy T, John VT, Culicchia F, Wisniewska-Becker A, Reiss K Abstract Fenofibrate, a well-known normolipidemic drug, has been shown to exert strong anticancer effects against tumors of neuroectodermal origin including glioblastoma. Although some pharmacokinetic studies were performed in the past, data are still needed about the detailed subcellular and tissue distribution of fenofibrate (FF) and its active metabolite, fenofibric acid (FA), especially in respect to the treatment of intracranial tumors. We used high performance liquid chromatography (HPLC) to elucidate the intracellular, tissue and body fluid distribution of FF and FA after oral administration of the drug to mice bearing intracranial glioblastoma. Following the treatment, FF was quickly cleaved to FA by blood esterases and FA was detected in the blood, urine, liver, kidney, spleen and lungs. We have also detected small amounts of FA in the brains of two out of six mice, but not in the brain tumor tissue. The lack of FF and FA in the intracranial tumors prompted us to develop a new method for intracranial delivery of FF. We have prepared and tested in vitro biodegradable poly-lactic-co-glycolic acid (...
Source: Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Tags: J Physiol Pharmacol Source Type: research