Mj. Fonseca et al., COATING LIPOSOMES WITH COLLAGEN (M(R)-50000) INCREASES UPTAKE INTO LIVER, Biochimica et biophysica acta. Biomembranes, 1279(2), 1996, pp. 259-265
Collagen-coated small unilamellar liposomes were prepared by incubatio
n of two hydrophobic derivatives of collagen (average M(r) 50 000) wit
h preformed vesicles. The introduction of hexyl and lauryl residues to
the collagen molecule improved by 10-fold the ability of collagen to
coat liposomes. In vitro stability of the different coated vesicles pr
epared, was studied by their ability to retain entrapped carboxyfluore
scein as a function of the time. Coated vesicles were clearly more sta
ble in vitro than control liposomes, except for those containing the l
auryl derivative in a protein/phospholipid weight ratio higher than 10
(-3). Vesicle clearance from circulation as well as tissue distributio
n were also determined. Pharmacokinetics (determined by both fluoresce
nce and radioactive techniques) were highly dependent on the injected
dose, phospholipids used and the content of collagen. Half-lives were
maximum for liposomes composed of saturated phospholipids injected at
a dose of 2 mu mol phospholipid. Besides, blood elimination of collage
n-containing vesicles was about 2-fold faster and liver uptake 1.5 to
2-fold higher than control liposomes.