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French patent application FR0603945 filed on May 3th, 2006 entitled “Nouveau procédé de concentration extemporanée et réversible de liposomes par addition contrôlée de cyclodextrines”
Sylvie LESIEUR
Geneviève LE BAS
Valérie BERNAT
Catherine RINGARD LEFEBVRE
Exclusive or non-exclusive licenses, Collaborative agreement
Physico-chimie, pharmacotechnie, biopharmacie a CNRS laboratory (UMR8612) in Paris, France, http://www.umr-cnrs8612.u-psud.fr/EN/KitSC/intro.htm
Liposomes are self-closing spherical particles that are composed of natural or synthetic amphiphilic lipid molecules. Their ability to entrap both water soluble and insoluble substances and deliver them to a desired environment is the basis of their use in drug delivery technologies. However, the high production cost of liposomes and encapsulation rate make these an important barrier in their using.
The team investigate a way to reduce cost associate with liposome production and find a way to increase encapsulation capacity.
The invention relates to new process for the concentration of liposome (able to contain any sorts of molecules) by controlled addition of Alpha-cyclodextrin. Alpha-Cyclodextrin is a cyclic oligosaccharide resulted from amidon molecules and able to trap hydrophobic molecules with its hydrophobic cavity.
This process works without any organic solvents addition, heating or energy. This process is stable and reversible by dilution; the liposome/α-cyclodextrin mixture can be lyophilised and then rehydrated. During the process there is no modification in the structure and composition of the liposomes.
There is a numerous advantages of this new process including easy to use, inexpensive and using for great volume. It’s an alternative for utra-centrifugation or ultra-filtration process.
The present invention may be used in pharmaceutics, in cosmetics and in food industry for liposome controlled concentration.
The process has been extended to different phosphatidylcholine-based liposomes to investigate the influence on one hand of the hydrocarbon chain length and insaturation degree of the lipid molecules and on the other hand of the liposome size. In all cases, liposome concentration is obtained, only the a-cyclodextrin/lipid molar ratio has to be adjusted to the structure of the lipid. This work is part of the V. Bernat’s PhD thesis defended in 2008.
Fundamental investigations have been undertaken to understand the mechanism of the liposome concentration process. Differential calorimetry, X-ray diffraction, electron microscopy and 1H NMR experiments have been performed to explain the a-cyclodextrinlipid interactions involved and to characterize the transient aggregates formed. Isothermal titration calorimetry as well as 31P NMR measurements are under way. The results obtained in their whole should be the subject of at least one publication in a scientific journal of high impact factor.
For further information, please contact us (Ref 00683-01)
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