Since a few years we have a collaboration with the Italian pharmaceutical
company Sigma-Tau in Pomezia (Roma). This company has developed hundreds
of carnitine derivatives, including some these compounds function well
as surfactants. One of the aim of the company is the application of such
carnitine surfactants as basis for the formation of vesicles that can be
used for drug delivery systems. One such system is PUCE, palmitoyl undecyl
carnitine ester, that forms spontaneously cationic vesicles in water.
In addition, the company is also interested in the commercialization
of a camptothecin derivative (CPT), a powerful drug against certain types
of tumor.
Over the last years - 2000 and 2001, first Cornelia Heiz (graduated
in 1999), then Dr. Jörg Heerklotz and Dr. Elisa Peroni have
been working in our lab in Zürich in a project aimed at preparing
CPT-containing vesicles from PUCE.
Mostly the injection method has been used for the preparation of PUCE
vesicles, and conditions have been found, under which very small (30-60
nm radius) vesicles that contained a therapeutically sufficient amount
of CPT could be prepared. Biological studies with animals have given very
promising results. This vesicle preparation obtained with the
injection
method has been compared with one prepared from a thin lipid film deposited
on glass by a classic vesicle formation method. In addition, comparison
is in progress between PUCE and POPC vesicles in terms of transport of
CPT and the biological activity.
Gene transfer experiments have been also carried out, utilizing a plasmid
containing the gene of a fluorescent protein as label for the transfection
efficiency.
To this aim, PUCE vesicles bearing a positive charge have proved to be
efficient vectors for DNA; these vesicles are being compared in terms of
transport efficiency with POPC liposomes containing variable amounts of
the classic cationic surfactant DDAB (dioctadecyldimethylammonium bromide).
Biological activity with PUCE liposomes again appears to be very promising.
One work that was initiated by Cornelia Heiz with liposomes as drug
delivery systems concerns liposomes as an aerosol preparation. This work
was carried out in collaboration with the “Kantonsspital” in Bern, in a
project aimed at finding alternative routes to methadon for drug addicts,
thus eliminating the use of syringes.
At the end of 2001 both Jörg Heerklotz and Elisa Peroni left the
group, and their work is now continued and developed by Simone Bufali and
Pasquale Stano. They have also the function of being responsible of the
two dynamic light scattering instruments we have in the group, and the
corresponding data elaboration.