Feasibility of drug targeting to the retinal pigment epithelium with biodegradable microspheres

There are several systems of delivering drugs to cells with phagocytic activity. We studied the possibility of targeting drugs to retinal pigment epithelial (RPE) cells with the use of surface-modified microspheres. A fluorescent dye, 1,4-bis[2-(5-phenyloxazolyl)]-benzene (POPOP), was incorporated into microspheres of poly(lactic acid) for use as a marker to evaluate drug delivery. Phagocytosis of the microspheres, with or without gelatin precoating, was carried out at 37 degrees C and 4 degrees C. The cell-incorporated fluorescence of POPOP was measured, and scanning electron microscopy was used to confirm phagocytosis. At 4 degrees C, no uptake of POPOP was noted; however at 37 degrees C, cell-associated fluorescence was observed to increase for up to 24 hr. In comparison with bare microspheres, gelatin precoating significantly enhanced phagocytosis (P < 0.001) at the same incubation times. These results suggested that drug delivery to RPE cells may be feasible by means of surface-modified polymer microspheres.