Biodegradable polymer microspheres for targeted drug delivery to the retinal pigment epithelium

The authors evaluated the feasibility of biodegradable polymer microspheres of poly (L-lactic acid) and poly(glycolic acid) to deliver a substance directly to the retinal pigment epithelial (RPE) cells. The microspheres encapsulated a fluorescent dye (rhodamine 6GX) that was used as a drug marker. The dye released from the microspheres was analyzed by spectrofluorophotometry in vitro. Microspheres were administered to cultured bovine RPE cells. Phagocytosis of the microspheres by RPE cells was studied by fluorescent microscopy and transmission electron microscopy. Intracellular release of the fluorescent dye was also evaluated after phagocytosis of the microspheres. A suspension of the microspheres was administered into the subretinal space via transvitreal approach with a glass micropipette in the rabbits in vivo. The release rate of the fluorescent dye was controllable by changing the molecular weight and the monomer composition of the copolymers in vitro. Microspheres were phagocytosed by RPE cells and the dye was released intracellularly during incubation. After subretinal delivery, the microspheres were degraded in the cytoplasm of the RPE, but the fragments were observed up to four weeks. The retinal architecture overlying the delivery site was well preserved. These results suggest that it is feasible to deliver substances directly to the RPE cells with the use of polymer microspheres without damaging the neural retinal structure. This drug delivery system may enable the functions of RPE cells to be modified pharmacologically.