PROLONGATION OF LIPOSOME CIRCULATION TIME BY VARIOUS DERIVATIVES OF POLYETHYLENEGLYCOLS

New lipid derivatives of polyethyleneglycol (PEG) have been synthesize d and tested for the ability to allow liposomes to evade uptake by the reticuloendothelial system (RES) and to prolong the circulation time of liposomes in mice, Liposomes were prepared from distearoylphosphati dylcholine (DSPC) and cholesterol (CH) (1:1, m/m) containing 6 mol% of various PEG-derivatives, The activity of the CH derivative of PEG (CH -PEG) in prolonging the circulation time of liposomes was proportional to the average molecular weight of PEG, i.e., 4800>2600>1700>800, alp ha-Methoxy-omega-(1,2-dioctadecenoyloxy glyceryl)polyoxyethylene (DO-P EG) 1000 and alpha-methoxy-omega-(1,2-ditetradecenoyloxy glyceryl) pol yoxyethylene (DT-PEG) 1000, in which PEG is directly linked to glycero l, prolonged the circulation time as effectively as distearoylphosphat idyl-N-(methoxy polyoxyethylene succinyl)-ethanolamine (DSPE-PEG), PEG -derivatives with a functional group at the PEG terminal, such as dist earoylphosphatidyl-N-(3-carboxypropionyl polyoxyethylene succinyl)etha nolamine (DSPE-PEG-COOH) and almitoylphosphatidyl)-omega-hydroxypolyox yethylene (DPP-PEG-OH), effectively prolonged the circulation time of liposomes, Incorporation of PEG-derivatives did not change membrane fl uidity even after treatment with serum, Furthermore, incorporation of PEG-derivatives into liposomes decreased uptake by J774 cells, a murin e macrophage-like cell line, in vitro, The newly synthesized PEG-deriv atives seem to prevent or reduce the interactions of liposomes with se rum protein and macrophages, resulting in enhanced stability and a pro longed circulation time.