T. Yuda et al., PROLONGATION OF LIPOSOME CIRCULATION TIME BY VARIOUS DERIVATIVES OF POLYETHYLENEGLYCOLS, Biological & pharmaceutical bulletin, 19(10), 1996, pp. 1347-1351
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.