Selective Nanovector Mediated Treatment of Activated Proinflammatory Microglia/Macrophages in Spinal Cord Injury

• DOI: 10.1021/nn4036014
• Publication Date: 2013-10-18T18:33:44Z
• Authors: Simonetta Papa; Filippo Rossi; Raffaele Ferrari; Alessandro Mariani; Massimiliano De P...; Ilaria Caron; Fabio Fiordaliso; Cinzia Bisighini; Eliana Sammali; Claudio Colombo; Marco Gobbi; Mara Canovi; Jacopo Lucchetti; Marco Peviani; Massimo Morbidelli; Gianluigi Forloni; Giuseppe Perale; Davide Moscatelli; Pietro Veglianese
• Keywords: Proinflammatory cytokine; Minocycline; Nanocarriers

Much evidence shows that acute and chronic inflammation in spinal cord injury (SCI), characterized by immune cell infiltration release of inflammatory mediators, is implicated development the secondary phase occurs after trauma worsening damage. Activation microglia/macrophages associated response appears to be a self-propelling mechanism leads progressive neurodegeneration persisting pain state. Recent advances polymer science have provided huge amount innovations leading increased interest for polymeric nanoparticles (NPs) as drug delivery tools treat SCI. In this study, we tested evaluated vitro vivo new nanocarrier: minocycline loaded NPs composed based on poly-ε-caprolactone polyethylene glycol. These are able selectively target modulate, specifically, activated proinflammatory subacute progression SCI mouse model. After minocycline-NPs treatment, demonstrate reduced activation proliferation around lesion site reduction cells with round shape phagocytic-like phenotype favor more arborized resting-like low CD68 staining. Treatment here proposed limits, up 15 days tested, stimulus microglia/macrophage activation. This was demonstrated expression cytokine IL-6 persistent traumatized site. The nanocarrier tool developed potential advantages over conventionally administered anti-inflammatory therapy, maximizing therapeutic efficiency reducing side effects.