Akut Omurilik Travmalarında Kullanılmak Üzere Nöroprotektif İlaç Yüklü Nanopartiküler İlaç Taşıyıcı Sistem Geliştirilmesi
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2015Yazar
Akyürek, Yasemin
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Methyl prednisolone sodium succinate (MPSS) is a
very hydrophilic synthetic glucocorticoid. Although it is usually used for its antiinflammatory
effects, it is still the only efficacy proven therapeutic agent which is used
in the treatment of spinal cord damage occurring after trauma. Due to the serious side
effects caused by high doses that need to be administered, MP administration after SCI
is highly criticized. In our study it is aimed to develop a nanoparticle-gel combined
drug delivery system for localization of MP on trauma site and eliminating dosedependent
side effects. For this purpose, MPSS loaded polycaprolactone nanoparticles
were developed and embedded in a fibrin gel formulation which is developed in the
context of this thesis. Optimum nanaoparticles with an average particle size of 185nm
and 7,9 % drug encapsulation efficiency were produced with nanoprecipitation method.
The in vivo efficiency of nanoparticle-gel system are evaluated on an acute spinal cord
injury rat model. The levels of inflammatory cytokines (interleukin-1β, interleukin-6)
and caspase-3 were quantified in traumatized spinal cord tissues for the assessment of
anti-inflammatory effects of the different formulations. Furthermore, the damage on
ultrastructural level was assessed by transmission electron microscopy. Regarding
inflammatory cytokine levels and histopathological damage, the developed NP-gel
system showed very similar efficacy results with systemic high dose of MPSS. It is
believed that the system developed and characterized in this study may be used as an
alternative for the safe and effective delivery of several other therapeutic molecules on
injured spinal cord cases.