pH sensitivity and plasma stability of liposomes containing N-stearoylcysteamine.
In this study, we investigated the pH sensitivity of different liposomal formulations containing 10 mol% N-stearoylcysteamine, as pH sensitive molecule. Liposome stability was monitored by determining the release of different entrapped water soluble molecules, 5,6-carboxyfluorescein (CF) being the marker of leakage mainly used. Small unilamellar vesicles composed of egg phosphatidylcholine (EPC) and N-stearoylcysteamine (9:1 molar ratio) incubated at 20 degrees C in citrate phosphate buffer released, at pH 6.8, 2.5 fold the amount of CF released at pH 7.4. The addition of plasma to the incubation medium and an increase of temperature to 37 degrees C led to significantly increased the CF release from EPC/N-stearoylcysteamine SUV, both at pH 7.4 and 6.8. The addition of cholesterol had a stabilizing effect on liposomal vesicles with respect to both temperature and plasma, without affecting pH sensitivity. In fact, at 37 degrees C and in 25% plasma the ternary mixture showed the highest CF release, as a consequence of the moderate acidification of the medium from 7.4 to 6.8. Thus, these liposome formulations are potentially a useful tool for specific drug delivery to pathological tissues such as tumours, inflammation sites and ischemic areas where it is known that a lowering of the pH can occur.
Cazzola
R
R
Department of Medical Chemistry and Biochemistry, University of Milan, Italy.
Viani
P
P
Allevi
P
P
Cighetti
G
G
Cestaro
B
B
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D002784:Cholesterol; D003543:Cysteamine / Q000031:analogs & derivatives*; D004337:Drug Carriers; D004355:Drug Stability; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005947:Glucose; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007700:Kinetics; D008027:Light; D008051:Lipid Bilayers / Q000097:blood* / Q000737:chemistry*; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D010713:Phosphatidylcholines / Q000737:chemistry*; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D013229:Stearic Acids
D004337:Drug Carriers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D008051:Lipid Bilayers; D008081:Liposomes; C109190:N-stearoylcysteamine; D010713:Phosphatidylcholines; D013229:Stearic Acids; D015060:1,2-Dipalmitoylphosphatidylcholine; C024098:6-carboxyfluorescein; D003543:Cysteamine; D002784:Cholesterol; D005947:Glucose