Uptake of liposomes by human retinal pigment epithelial cells in culture

Abstract

Summary form only received as follows: The phagocytic uptake of several liposome compositions by human retinal pigment epithelial (RPE) cells in culture was examined. The endocytic uptake of different Iiposome preparations was quantitatively measured for RPE, RAW 264.7 and rabbit dermal fibroblasts. RAW 264.7 is a transformed macrophagic murine cell line used as a positive control while rabbit dermal fibrocytes are a cell line developed for in vivo animal models of PVR. Measurement of the internalization of a non-degradable radiolabeled cholesterol analog incorporated in the liposome bilayer was used to quantify the uptake of liposomes. Fluorescence microscopy was used to confirm the internalization of the vesicles. The composition of liposomes most avidly ingested by RPE most closely resembled shed rod outer segments (ROS). The most actively phagocytized liposomes like the ROS plasma membrane contained phosphatidylserine and lacked cholesterol. Additionally, a greater uptake of the large multiluminar vesicles ranging in size from 0.20 /spl mu/m to 2 /spl mu/m compared to smaller vesicles extruded through a 0.22 /spl mu/m filter demonstrated liposomal size influenced the uptake process. The larger vesicles were closer in size to naturally occurring ROS. Uptake by RPE was significantly lower than observed with RAW 264.7 cells, but greater than exhibited by rabbit dermal fibroblasts. These findings appear to have important implications regarding the use of liposomes as drug carriers for the treatment of proliferative vitreoretinopathy and the study of phagocytosis by RPE.