Preparation of Albumin Microspheres Grafted Galactose Residues Through Polyethylene-Glycol Spacers,Release Behavior of 5-Fluorouracil from Them,and Their Lectin-Mediated Aggregation

Small-sized albumin gel microspheres, MSs, containing 5-fluorouracil (5FU) with targeting moieties on their surfaces (average diameter: 1.5 μm) were prepared by the glutaraldehyde crosslinking method and suspension technique. Since galactose is known to interact specifically with the asialoglycoprotein receptor on hepato-cyte, the galactose residues were introduced on the surface of MSs as the targeting moieties for hepatoma through polyethylene glycol (PEG) spacers. PEG spacers were employed to depress the immu-nogenicity of albumin, to keep the mobility of the galactose residues, and to heighten the distributive stability of the MSs in aqueous solution. It was confirmed by ESC A analysis that the PEG chains were introduced onto the surfaces of MSs. The amount of galactose residues introduced to MS were estimated to be 0.013 wt%. The intra-MSs aggregation was observed by the addition of Ricinus Communis Agglutinin I (RCA120) into the MS suspension, and then the aggregation of MSs was dissociated by addition of free lactose. Moreover, by incubation of the MSs with human hepatoma HLE cells, the phenomena of MS's specific binding onto HLE cell surfaces and phagocytosis of MSs by HLE cells were observed. These results suggested that the galactose residues on the surface of MSs were recognized with the galactose receptors on hepatoma cell surfaces. The release rate of 5FU from MSs was investigated in vitro in physiological saline at 37OC. About 90% of encapsulated 5FU were found to be released from MSs through incubation for 8 h.