CHARACTERIZATION OF BIOTINYLATED LIPOSOMES SENSITIVE TO TEMPERATURE AND PH - NEW TOOLS FOR ANTICANCER DRUG-DELIVERY

We describe a liposome formulation characterized by sensitivity to con current and small temperature and pH changes. Liposome permeability wa s assessed by monitoring the release of entrapped carboxyfluorescein ( CF), using a fluorescence dequenching technique. The thermotropic beha vior of the liposomes was investigated by differential scanning calori metry. After 2 h at 37 degrees C in fetal calf serum, liposomes compos ed of a mixture of dipalmitoyl phosphatidylcholine/cholesterol/GM1 gan glioside/biotinoyl-dipalmitoyl phosphatidylethanolamine (100:20:6:0.25 molar ratio) released 8% CF at pH 7.4 and 12% CF at pH 6.7. At 41 deg rees C the leakage was 72% at pH 7.4 and almost complete (99%) at pH 6 .7. The pH and temperature sensitivity, with maximal release when the two circumstances occurred simultaneously, was confirmed by entrapping calcein or [C-14]glucose. The reasons for the bilayer sensitivity and the conditions for in vivo drug delivery are discussed.