Læknablaðið : fylgirit - 03.01.2017, Blaðsíða 79

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
LÆKNAblaðið/Fylgirit 91 2017/103 79
from the inflamed site is necessary for resolution of inflammation, decr-
eased secretion of cytokines that are important for neutrophil survival
(like TNF-α and GM-CSF) may be involved in the mechanism by which
omega-3 PUFA enhance resolution of inflammation.
V 57 Natural killer cells play an essential role in resolution of
antigen-induced inflammation in mice
Ósk Anuforo1, Stefanía P. Bjarnarson1, Hulda Jónasdóttir2, Martin Giera2, Ingibjörg
Harðardóttir3, Jóna Freysdóttir1
1Dept of Immunology, Landspitali-The National University Hospital of Iceland / University
of Iceland, 2Center for Proteomics and Metabolomics, Leiden University Medical Center,
3Biohemistry and Molecular Biology, Faculty of Medicine, University of Iceland
oua@hi.is
Introduction: NK cells have been implicated in resolution of allergic
airway inflammation. This study examined the role of NK cells in
resolution of inflammation in an antigen-induced peritonitis.
Methods and data: Mice were immunized twice with methylated BSA
(mBSA) and inflammation induced by intraperitoneal injection of mBSA.
They were injected intravenously with an NK cell depleting antibody
(anti-asialo GM1, αASGM1) or a control antibody 24 h prior to peritonit-
is-induction. Peritoneal exudates, spleen and draining lymph nodes were
collected and cryosections stained by immunofluorescence and peritoneal
cells and soluble mediators analyzed by flow cytometry, ELISA and LC-
-MS/MS.
Results: The number of peritoneal neutrophils 12 h after induction of in-
flammation was higher in the αASGM1-injected mice than in the control
mice. The number of neutrophils was still high in the αASGM1-injected
mice when they had returned to baseline in the control mice. Peritoneal
concentrations of the neutrophil regulators G-CSF and IL-12p40 were
higher at 12 h in the αASGM1-injected mice than in the control mice,
whereas concentrations of lipid mediators implicated in resolution of
inflammation, i.e. LXA4 and PGE2, were lower. Reduced apoptosis was
detected in draining lymph nodes and spleens from the αASGM1-injected
mice compared with that in the control mice and lower numbers of perito-
neal NK cells expressing NKp46 and NKG2D, receptors implicated in NK
cell-induced neutrophil apoptosis.
Conclusions: These results indicate a crucial role for NK cells in resolution
of antigen-induced inflammation and suggest their importance in temper-
ing neutrophil recruitment and maintaining neutrophil apoptosis.
V 58 Design of experiments approach for structural optimization of
antibacterial and hemolytic properties of chitosan derivatives
Priyanka Sahariah1, Bergþóra S. Snorradóttir2, Martha Á. Hjálmarsdóttir2, Ólafur E.
Sigurjónsson3, Már Másson2
1Pharmaceutical Sciences, University of Iceland, 2University of Iceland, 3Landspitali University
Hospital
prs1@hi.is
Introduction: Design of Experiments (DOE) is a systematic method for
planning and analyzing the outcome of experiments and describing the
relationship between the factors affecting an experiment and the outcome
(responses). In the current study, the DOE approach was used to obtain
the minimum number of compounds containing various proportions of
cationic and hydrophobic groups that would have maximum influence on
the activity/toxicity of the biopolymer, chitosan.
Methods: MODDE, a specialized software for planning and analyzing
the results of a DOE study, was used to design the experiments, create a
model and analyze the results. The three experimental parameters were
the three functional groups namely the N,N,N-trimethyl group, N-acetyl
group and N-stearoyl group, which were introduced into the polymer at
specific ratios in ‘one-pot synthesis’ utilizing the TBDMS protected chitos-
an. The antibacterial activity (MIC) towards the Staphylococcus aureus and
Escherichia coli, hemolytic activity (HC50) towards human red blood cells
and solubility of the chitosan derivatives were used as the responses in
the model.
Results: The refinement of the model led to improvement of the statistical
significance and predictive power of the model, which showed that the
trimethyl group is the most influential factor for enhancement of aqueous
solubility and antibacterial activity of the derivatives towards Stap-
hylococcus aureus and Escherichia coli, while N-acetyl and N-stearoyl group
remained less significant.
Conclusion: The results led us to the conclusion that using structure as a
variant, design of experiments can be successfully utilized for the develop-
ment of structure-activity relationship of this biomaterial.
V 59 Micro-encapsulated doxycycline containing buccal films with
improved stability, enhanced mucoadhesion and residence times
Venu Gopal Reddy Patlolla1, Þórdís Kristmundsdóttir1, Peter Holbrook2
1Faculty of Pharmaceutical Sciences, 2Faculty of Odontology, University of Iceland
vgr1@hi.is
Introduction: Mucoadhesive buccal films are an efficient and alternative
drug delivery systems to the enteral route, which can be utilized to deliver
drugs to both local as well as systemic circulation. They form a protective
barrier over the inflamed mucosa, which prevents the further exacerbation,
but the drawbacks include poor retention at the applied site due to dislod-
gement from tongue activity, rapid disintegration of the films and drug burst
release. All the drawbacks were addressed by incorporating micro-particles
into the buccal films and their physicochemical properties were studied.
Methods: The films were prepared using a solvent casting method, the
micro-particles were prepared using a spray dryer, the micro-particle size
was evaluated using a microscope and the morphological characteristics
were analysed by scanning electron microscopy. The drug-excipient inter-
action was evaluated using Differential scanning calorimetry(DSC), the in
vitro release times were accessed using the USP paddle over disc method,
the permeation studies were carried out with an artificial membrane and
the mucoadhesion studies were evaluated with the texture analyzer.
Results: A prolonged and uniform drug release was achieved and also
improved the stability of the active component. The work of mucoadhes-
ion was improved as the individual micro-particles possess more surface
area of exposure to the mucus membrane and marked difference in the in
vitro release times for the films containing micro-particles was observed.
Conclusions: The study showed that the incorporation of micro-particles
improved the stability, formulation retention time and enhanced the
mucoadhesion capacity, but the uniform drug distribution needs to be
further addressed.
V 60 Exopolysaccharides from C. aponinum enhance cytokine and
chemokine production of HaCaT cells
Vala Jónsdóttir1,2,3, Ása Guðmundsdóttir2,3,4, Ingibjörg Harðardóttir3, Jóna
Freysdóttir1,2,3
1Faculty of Medicine, University of Iceland, 2Department of Immunology and 3Centre for
Rheumatology Research, Landspitali, 4Faculty of Pharmaceutical Sciences
vaj16@hi.is