Starch acetates are novel biodegradable polymers which undergo slower degradation and swelling than native starch. Retinal pigment epithelium (RPE) is an important target tissue in ocular treatment. The cellular uptake of starch acetate microparticles and degradation of starch acetate by cultured human RPE-cell line (D407) was examined. Calcein-containing starch acetate microparticles were prepared by a modified water-in-oil-in-water double-emulsion technique. The cellular uptake of the starch acetate microparticles was analysed using flow cytometry and confocal microscopy. Degradation of starch acetate films by the homogenate of lysed RPE cells was determined by gel permeation chromatography. The effect of the microparticles on RPE cell viability was determined by the MTT colorimetric assay. The mean diameter (D50%) of microparticles was 11 microm. During 3-h incubation in RPE-cell culture, 8.1 +/- 0.8% of D407 cells took up starch acetate microparticles. Confocal microscopy confirmed the internalisation of microparticles. Incubation of the starch acetate film in the RPE-cell homogenate considerably decreased the molecular weight of starch acetate in the film during 24 h. The viability of cultured RPE cells was at least 82% after 24-h incubation with the microparticles. The present results show that the starch acetate microparticles are taken up by the RPE cells and the polymer can be degraded by the enzymes in these cells. Starch acetate microparticles may be suitable for drug delivery to the RPE.