Abstract
We examined the ability of polyethyleneglycol in avoiding reticuloendothelial system (RES) from colloid chemical view points. In this respects, we examined the effects of the dose on the distributions, in vivo. The thickness of the fixed aqueous layer(TAL) around liposomes modified with 1-(monomethoxy polyethyleneglycol)-2, 3-dipalmitoyl glycerol(PEG-DPG) containing adriamycin (ADR) (PEG-LADR : 5 mol%) was determined to be 1.8 nm, while those around conventional plain liposomal ADR (PLADR) and PEG (×2)-LADR (PEG : 10 mol%) were 0.3, 1.6 nm, respectively. The thickness of the fixed aqueous layer around PEG-DPG modified liposomes was not dependent on PEG-DPG mol content. The RES avoiding was dependent on TAL. In vivo study, the prolonged circulation time in the blood, decrease in the distribution to the heart and RES avoiding was confirmed both in high (ADR 7.5 mg/kg, i.v.) and low (ADR 2.5 mg/kg, i.v.) dose study. In the liver, in 7.5 mg/kg dose, the ADR concentrations by liposomes were higher than that of ADRsol while 2.5 mg/kg dose, the ADR concentrations by liposomes were lower than that of ADRsol. Thus, the RES uptakes were affected by ADR dose as well as TAL. Therefore, distribution study of liposomes must be investigated at doses as close to the clinical doses as possible.
