ABSTRACT
The possibility to control the fate of the cells responsible for secondary mechanisms following spinal cord injury (SCI) is one of the most relevant challenges to reduce the post traumatic degeneration of the spinal cord. In particular, microglia/macrophages associated inflammation appears to be a self-propelling mechanism which leads to progressive neurodegeneration and development of persisting pain state. In this study we analyzed the interactions between poly(methyl methacrylate) nanoparticles (PMMA-NPs) and microglia/macrophages in vitro and in vivo, characterizing the features that influence their internalization and ability to deliver drugs. The uptake mechanisms of PMMA-NPs were in-depth investigated, together with their possible toxic effects on microglia/macrophages. In addition, the possibility to deliver a mimetic drug within microglia/macrophages was characterized in vitro and in vivo. Drug-loaded polymeric NPs resulted to be a promising tool for the selective administration of pharmacological compounds in activated microglia/macrophages and thus potentially able to counteract relevant secondary inflammatory events in SCI.
Subject(s)
Drug Carriers/administration & dosage , Microglia/metabolism , Nanoparticles/administration & dosage , Polymethyl Methacrylate/administration & dosage , Spinal Cord Injuries/metabolism , Animals , Behavior, Animal/drug effects , Carbocyanines/administration & dosage , Carbocyanines/chemistry , Cell Survival/drug effects , Cells, Cultured , Coloring Agents/administration & dosage , Coloring Agents/chemistry , Drug Carriers/chemistry , Female , Hydrogels , Lipopolysaccharides , Macrophages/drug effects , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Microglia/drug effects , Nanoparticles/chemistry , Polymethyl Methacrylate/chemistry , Spinal Cord/metabolismABSTRACT
In the injured spinal cord, chondroitin sulfate proteoglycans (CSPGs) are the principal responsible of axon growth inhibition and they contribute to regenerative failure, promoting glial scar formation. Chondroitinase ABC (chABC) is known for being able to digest proteoglycans, thus degrading glial scar and favoring axonal regrowth. However, its classic administration is invasive, infection-prone and clinically problematic. An agarose-carbomer (AC1) hydrogel, already used in SCI repair strategies, was here investigated as a delivery system capable of an effective chABC administration: the material ability to include chABC within its pores and the possibility to be injected into the target tissue were firstly proved. Subsequently, release kinetic and the maintenance of enzymatic activity were positively assessed: AC1 hydrogel was thus confirmed to be a feasible tool for chABC delivery and a promising device for spinal cord injury topic repair strategies.
