Preparation and characterization of 5-fluorouracil-loaded poly(ε-caprolactone) microspheres for drug administration

Microspheres of 5-fluorouracil-loaded poly(epsilon-caprolactone) (PCL) were prepared by spray-drying procedure. The degradation characteristics and 5-fluorouracil release in vitro as well as in vivo were investigated. The average molecular weight, weight loss, crystallinity and morphology of microspheres were determined using GPC, DSC, and SEM, at different times during the in vitro degradation process. The size distribution of the microspheres indicated that most of the particles were smaller than 3 mum. A 30% weight loss as well as an increase of crystallinity were observed on day 330 of incubation. The percentage of entrapment efficiency of 5-FU was 49% (44 mug of drug/mg of microspheres). The in vitro total release of 5-FU took place in 8 days. Determination of plasma 5-FU concentration in vivo using s.c. injection of 5-FU-Ioaded microspheres in Wistar rats by HPLC with analysis of data using a noncompartmental model showed drug in plasma 18 days after administration with a maximum drug concentration of 1.5 mug/ml at 96 h. Pharmacokineticallly, a significant increase of AUC and, MRT of 5-FU with regard to the administration of the drug in solution. Scanning electron microscopy and histological studies indicated that the microspheres were surrounded by connective tissue and inflammatory processes were not evident. As a result of these characteristics, the 5-FU-loaded PCL microspheres could be used for drug delivery. (C) 2004 Wiley-Liss, Inc.