Characterization of biotinylated liposomes sensitive to temperature and pH: new tools for anti-cancer drug delivery.
We describe a liposome formulation characterized by sensitivity to concurrent and small temperature and pH changes. Liposome permeability was assessed by monitoring the release of entrapped carboxyfluorescein (CF), using a fluorescence dequenching technique. The thermotropic behavior of the liposomes was investigated by differential scanning calorimetry. After 2 h at 37 degrees C in fetal calf serum, liposomes composed of a mixture of dipalmitoyl phosphatidylcholine/cholesterol/GM1 ganglioside/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 degrees 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 [14C]glucose. The reasons for the bilayer sensitivity and the conditions for in vivo drug delivery are discussed.
Ferraretto
A
A
Department of Medical Chemistry and Biochemistry, University of Milano, Italy.
Sonnino
S
S
Soria
M R
MR
Masserini
M
M
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001710:Biotin / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D010539:Permeability; D012680:Sensitivity and Specificity; D013696:Temperature
D000970:Antineoplastic Agents; D008081:Liposomes; D001710:Biotin