Polymeric microparticles for fenretinide administration

This study describes the production and characterization of biocompatible and biodegradable microparticles containing fenretinide (4HPR), designed for subcutaneous administration. The influence of type of polymer and production parameters was studied on microparticle characteristics and 4HPR release modality. Microparticles were made using solvent evaporation procedure and different polymers, such as polymethacrylates (Eudragit RS 100) and polyesters, namely poly(DL-lactide), DL-PLA, poly(DL-lactide-co-glycolide) 50:50, DL-PLGA 50:50 and poly(DL-lactide-co-glycolide) 75:25, DL-PLGA 75:25. 4HPR was encapsulated in polyester microparticles with efficiency values above 88 % w/w. In order to compare degradation characteristics of DL-PLA, DL-PLGA 50:50 and DL-PLGA 75:25 microparticles, in vitro degradation experiments simulating in vivo condition were carried out up to 30 days. Only DL-PLGA 50:50 microparticles showed significant changes in their morphology, whereas DL-PLA and DL-PLGA 75:25 remained almost intact after the same period of time. This different degradability is attributable both to polymer type and molecular weight. In vitro release experiments performed by dialysis method and HPLC, demonstrated that 4HPR is slowly released from microparticles. In particular the slowest kinetic was obtained by DL-PLGA 50:50. Moreover 4HPR chemical stability in microparticles was studied, demonstrating that DL-PLA microparticles maintained in the light at room temperature retained 100% of the 4HPR titer even after 3 months. At last the effect on cell growth of 4HPR containing microparticles have been tested on in vitro cultured erythroleukemia K-562 cells. The obtained data indicate that DL-PLGA 50:50 microparticles are able to almost double the efficacy of 4HPR, with respect to the free drug.