Læknablaðið : fylgirit - 03.01.2017, Blaðsíða 82

X V I I I V Í S I N D A R Á Ð S T E F N A H Í
F Y L G I R I T 9 1
82 LÆKNAblaðið/Fylgirit 91 2017/103
ed, especially parabens with long alkyl chains, due to their low aqueous
solubility. Complexation of parabens with CDs such as αCD, βCD and
hydroxypropyl-βCD has been described but no data is available on the
γCD effect on the solubility of long chain parabens.
Methods: The phase-solubility profiles of four parabens (i.e. methyl-,
ethyl-, propyl- and butylparaben) were determined. Solutions from the
phase-solubility studies were also used to determine the cac values of γCD
using permeation techniques. Moreover, the effect of mixed parabens on
the cac values of γCD were investigated.
Results: The inclusion complexes of four paraben/γCD show BS type of
phase-solubility profiles. Moreover, the cac values of γCD in aqueous
solutions containing ethyl-, propyl- and butylparaben/γCD inclusion
complex solutions decreased while methylparaben did not affect the cac.
Furthermore, from the cac values, it can be concluded that the promoted
effect on self-assemble in γCD was in the order butyl- > propyl- > ethyl >
methylparaben.
Conclusion: Paraben form inclusion complexes with γCD. The tendency
of parabens to form γCD complexes depends on their alkyl chain length
(i.e. the longer the higher tendency). While solubility of parabens was
increased by complexation with γCD, formation of γCD aggregates was
promoted by presence of parabens. Mixture of parabens show synergistic
effect on the aggregate formation, especially mixtures of two parabens. It
is worth to note that parabens can promote self-assemble aggregation of
γCD and can cause precipitation during long term stability studies.
V 68 Immunomodulatory effects of fractions from the sponge
Halichondria sitiens
Jón Þ. Óskarsson1,2,3, Di Xiaxia4, Sesselja Ómarsdóttir4, Ingibjörg Harðardóttir2, Jóna
Freysdóttir1,2,3
1Faculty of Medicine, University of Iceland, 2Department of Immunology, and 3Centre for
Rheumatology Research, Landspitali-The National University Hospital of Iceland, 4Faculty of
Pharmaceutical Sciences, University of Iceland
jonthorir@gmail.com
Introduction: Marine sponges produce a wide range of bioactive meta-
bolites and there is an increased focus on exploring them as a source of
natural products. The objective of this study was to obtain fractions and
pure compounds from the sponge Halichondria sitiens and determine their
anti-inflammatory properties.
Materials and methods: Fractionation of extracts from H. sitiens was
carried out using solvent partitioning and the active fractions obtained
were fractionated further by size and polarity. Human monocyte-derived
dendritic cells (DCs) were matured with TNF-α and IL-1β and stimulated
with LPS for 24h in the presence or absence of fractions/compounds.
The effects of the fractions/compounds on maturation and activation
of the DCs were evaluated by measuring their secretion of cytokines
by ELISA and expression of surface molecules by flow cytometry.
Results: Of the more than 70 fractions obtained from H. sitiens eight
showed promising immunomodulatory effects. A few pure compounds
were identified but those tested did not have immunomodulatory effects.
The eight fractions all decreased DC secretion of IL-12, IL-27, IL-6 and IL-10
without affecting expression of HLA-DR and CD86. The reduction in IL-12
and IL-27 production was more than 50%, that of IL-6 20-40% and of IL-10
40-60% when compared to controls. One of the fractions affected the morp-
hology of the DCs causing them to take on an elongated or a pointed shape.
Conclusions: These results demonstrate that H. sitiens contains several
bioactive compounds that may reduce the ability of DCs to activate Th1
and/or Th17 cells and have possible applications in the treatment of au-
toimmune disease.
V 69 Experimental investigation and numerical modelling of drug
release and diffusion through soft contact lenses
Svetlana Solodova1, Kristinn Guðnason2, Bergþóra S. Snorradóttir1, Sven Th.
Sigurðsson2, Fjóla Jónsdóttir2, Már Másson1
1Faculty of Pharmaceutical Science, 2Faculty of Industrial Engineering, Mecha, University of
Iceland
svetlana@hi.is
Introduction: Ophthalmic drug delivery by soft contact lenses (SCL)
is more effective due to direct location on the cornea which results in a
high bioavailability of least 50% compared to about 1-5% for eye drops.
Hydrogel lenses are made from water-swollen, cross-linked, hydrophilic
polymers. These polymeric systems are expected not only to improve the
water content of the SCL but the permeability to oxygen, which are crucial
properties. Therefore, in the last decades, this direction has wide research
interest.
Methods and data: The commercial soft contact lenses used in this study
are Etaficon A (1-Day acuvue moist, J&J). Experimental study was carried
out by Franz diffusion cells. The diffusion and release profiles of Na-
diclofenac, a model drug, were measured by HPLC-analysis.
Results: Various conditions of drug release and diffusion experiments,
such as different concentrations of drug solutions and different temper-
atures throughout SCLs were examined. A numerical model that can be
used to model one dimensional multi-layer system was constructed and
validated by comparison with experimental data.
Conclusions: It was found that the concentration of drug and tempera-
ture affects the drug uptake in SCL and release from lenses. It is noted
that diffusion increase with rise in temperature for each concentration
solution. Quantity of diffusant independent of temperature at the end
of experiment, diffusion rate is changed only. The numerical model
constructed and it has a good agreement with experimental data and can
be used as a design tool for the development such ophthalmic delivery
system as SCLs.
V 70 Vasoldilation of acetylicylic acid on uterne arteries in
rats:clarifying prophylactic effects in preeclampsia
Helga Helgadóttir1, Teresa Tropea2, Sveinbjörn Gizurarson1, Maurizio Mandala2
1Faculty of Pharmaceutical Sciences, 2Cellular Biology, University of Calabria
heh37@hi.is
Introduction: Preeclampsia (PE) is one of the major reason for morta-
lity and morbidity of mothers, fetuses and neonates. Today high risk
pregnancies are recommended to take low-dose acetylsalicylic acid
(LD-ASA). Mechanism of LD-ASA in PE is not known, but by ana-
lysing results from published articles it seems that time of onset
may have major influence on the efficacy. The objectives of this stu-
dy was to determine whether ASA and it´s major metabolite salicylic
acid (SA) can induce a direct vasodilation on uterine arteries in rats.
Methods and data: Uterine (UA) and mesenteric arteries (MA) from
non-gravid and 20 days gravid rats were mounted in an arteriograph
organ bath and pre-contracted with phenylephrine to produce 40-50%
reduction in baseline. ASA and SA dose response was then tested by
adding the test drugs into the physiological salt solution superfusing
the arteries. Direct vasodilation effect was then recorded accordingly.