COATING LIPOSOMES WITH COLLAGEN (M(R)-50000) INCREASES UPTAKE INTO LIVER

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.