Chemical degradation of liposomes by serum components detected by NMR.
Interaction between serum components and liposomes is an oxygen-dependent exothermic process. We studied the interaction of 100 nm extruded liposomes (bearing positive, negative or no charge) with foetal calf serum by 1H NMR and 13C NMR, in order to further our understanding of these reactions. Studies of aqueous or organic extracts obtained after 2 h, 1 day or 1 week, showed hydrolysis to be a degradation process concomitant with the interaction with serum. Oxidation was identified as additional to hydrolysis in the process of degradation. Oxidation produced aldehydes, acids and alcohols, although aldehydes and alcohols were prone to further decomposition and only appeared transiently. Alkenes and other oxidized compounds predominated in those products derived from oxidation. In stearylamine-containing liposomes some aldehydes and a nitroderivative were found as degradation products. Such metabolites are apolar and their presence might explain the intrinsic toxicity of this kind of liposome in cell cultures. The work described in the present study revealed the chemical degradation of liposomes in the serum used. In all cases the results obtained were compared with liposomes not incubated with serum.
Foradada
M
M
Department de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Spain.
Pujol
M D
MD
Bermúdez
J
J
Estelrich
J
J
D000447:Aldehydes / Q000097:blood; D000588:Amines / Q000097:blood; D000818:Animals; D002247:Carbon Isotopes; D002417:Cattle; D003470:Culture Media; D006868:Hydrolysis; D008054:Lipid Peroxides / Q000032:analysis; D008081:Liposomes / Q000097:blood* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000447:Aldehydes; D000588:Amines; D002247:Carbon Isotopes; D003470:Culture Media; D008054:Lipid Peroxides; D008081:Liposomes; D017392:Thiobarbituric Acid Reactive Substances; C009317:stearylamine