Akut Omurilik Travmalarında Kullanılmak Üzere Nöroprotektif İlaç Yüklü Nanopartiküler İlaç Taşıyıcı Sistem Geliştirilmesi

Abstract

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.