Immune modifying effect of drug free PLGA nanoparticles on the course of experimental autoimmune neuritis (EAN)

Abstract

Experimental autoimmune neuritis (EAN) animal model mimics the human Guillain-Barre syndrome (GBS), an autoimmune disease of demyelination and inflammation of peripheral nerves. Despite advancement in clinical management and provision of palliative treatment to GBS patients, they cannot alleviate the severity of disease. In recent studies, infusion of cargo free nanoparticles (NPs), derived from biodegradable poly (lactic-co-glycolic) acid (PLGA) mitigated the severity of clinical symptoms of inflammatory disease models by reducing the migration of inflammatory monocytes at the inflammatory site. <br /> The aim of this study was to determine the therapeutic efficacy of PLGA based NPs on the disease course of EAN. Five in-vivo experimental studies were conducted to evaluate the therapeutic efficacy of NPs. Preventive dose of 9 mg/kg of NP-PVA500 was administered daily into the tail vein before the onset of symptoms. NP treatment significantly reduced the trafficking of inflammatory monocytes at inflammatory loci and promoted tissue repair. <br /> Early onset treatment with a similar dose of NP-PVA500 nm also reduced the clinical severity of EAN and the perivascular infiltration of monocytes into the particle treated sciatic nerves of rats. Therapeutic treatment with two different sized NPs (NP-PVA500, NP-PVA130) also mitigated the severity of disease and reduced the perivascular migration of inflammatory cells. NP infusions diverted the circulating monocytes towards the spleen thereby abrogating the inflammatory response. Therapeutic treatment with NP-PVA130 at the early onset of EAN also modulated the local immune response in the peripheral nerves of NPs treated animals by reducing the expression of proinflammatory markers (CD68, IL-1β, TNF-α) and elevated the expression levels of anti-inflammatory markers (CD163). A shift towards M2 in the balance of M1/M2 macrophage expression has been observed with nanoparticle treatment. <br /> A clear dose-dependent attenuation in the severity of EAN disease was observed when treated with NP-PVA130. Surfactant and polymer modified NPs reduced the clinical severity of EAN. Results from this study suggested that NPs can be tuned that they can efficiently modulate the circulating monocytes, which is critical to halt the initial inflammatory response. Interestingly, these PLGA based nanoparticles do not need an active pharmaceutical drug. <br /> This study highlighted the importance of cargo-free NPs towards a safe, specific and cost-effective treatment approach to modulate the inflammatory monocytes mediated pathology in various inflammatory disorders and also provided a first hint in view of a potential modulatory role on M1/M2 balance. A clear understanding of mechanism of NPs mediated immunomodulation and identification of key aspects (composition, dose, roue of administration and physicochemical properties) triggering the therapeutic effects can open a new arena for formulation scientists in choosing appropriate NPs based therapies.