Book of abstract 2008

Advantage of nanoparticles to deliver resveratrol into the cells
K. Teskač1, C. Caddeo2, J. Kristl1
1University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia; 2University of Cagliari, Dept. Farmaco
Chimico Tecnologico, Cagliari, Italy
Several studies have been demonstrated that polyphenolic compound resveratrol (RSV)
exerts striking cancer chemopreventive activity. What is more, investigations of resveratrol
biological effects exposed out its dual action, as it has been reported to participate in
prosurvival as well as prodeath cellular mechanisms, depending on cellular conditions,
specific cell molecular settings and the concentration used. Additionally, low solubility
and physical instability makes RSV real technological and medical challenge.
Thus, to allow RSV controlled release at the target site over a prolonged period of time
and to protect it from light or other degradative processes solid lipid nanoparticles (SLN)
with loaded RSV were prepared. Effects of RSV on morphology of the treated cells and
the localization of nanoparticles were investigated. Parallel their metabolic activity of
HEK 293 was determined and compared with results obtained with RSV alone. Ability
of test dispersions to cope with stress situation (UV-B light) was also checked.
In non radiated as also in radiated cells free RSV at 10 μM was well accepted by the cells,
while RSV at 100 μM cause an arrest in cell proliferation.
The effect of loaded SLN was expressed different regarding the treatment-following
conditions (non radiation or radiation). Interestingly, in non radiated cells treated with
RSV-loaded nanoparticles a significant increase of the metabolic activity was seen,
irrespective of RSV’s concentration and also elimination of the RSV’s cytotoxicity at 100
μM was observed.
However, RSV in lipid nanoparticles at 10 μM lost their beneficial effect when used on
radiated cells. Thus promotion of cell proliferation under stress conditions caused by UV-
B light
p44
was obtained only with high amount of RSV (100 μM) loaded in nanoparticles.
Above results are supported also by fluorescence pictures that have showed any detectable
alterations on cell morphology after their treatment with almost all test dispersions,
exception is only RSV alone at 100 μM leading to the strange shape of nuclei surrounded
with degradable or completely disappeared actin.
Ours results stressed out an importance of RSV’s concentration used to achieve protective
effect in normal cells, which can be transformed into cancer cells when exposed to the
stress condition (radiation). Cell destruction can be prevented only with higher amount
of RSV, which is unfortunately two-edged. However, loading of RSV into solid lipid
nanoparticles proved to be the most cell-benefit decision. Slowly releasing of RSV from
nanoparticles prevented the cells before a massive cellular distribution of RSV that can
lead to its destroyable pro-oxidative effect. Amount of released RSV is just enough to cope
with the oxidative stress and thus cell ability to survive is increased.
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