The use of fluorescence resonance energy transfer to study the disintegration kinetics of liposomes containing lysolecithin and oleic acid in rat plasma.
OBJECTIVE
To validate Fluorescence Resonance Energy Transfer (RET) as method to monitor disintegration of fluorescently labeled liposomes varying in lysolecithin/oleic acid (equimolar) content, lysolecithin fatty acid composition and vesicle size in rat blood plasma and buffer.


METHODS
NBD-PE and Rho-PE were used for RET. The measurements were performed on a Perkin Elmer LS-50 spectrofluorimeter. Liposomes were prepared by the extrusion method.


RESULTS
Analysis of the RET data was optimised using a fitting procedure to correct for fluorescence interference by plasma. The disintegration patterns of liposomes could be described by a biexponential decay model. Disintegration rate increased at increasing lysolecithin/oleic acid content and decreasing size. In contrast, all liposomes showed no disintegration in buffer.


CONCLUSIONS
RET is a suitable method to monitor liposome disintegration in non-diluted plasma. Rate and extent of liposome disintegration increases at decreasing liposome size and increasing lysolecithin/oleic acid content.
Madörin
M
M
Pharmaceutical and Analytical Development, Novartis AG, Basel, Switzerland. mmadoerin@weleda.ch
van Hoogevest
P
P
Hilfiker
R
R
Leuenberger
H
H
D000818:Animals; D004735:Energy Transfer; D008081:Liposomes / Q000097:blood / Q000493:pharmacokinetics*; D008244:Lysophosphatidylcholines / Q000097:blood / Q000493:pharmacokinetics*; D019301:Oleic Acid / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D013050:Spectrometry, Fluorescence / Q000379:methods
D008081:Liposomes; D008244:Lysophosphatidylcholines; D019301:Oleic Acid