Nanomedicine and its Application in Treatment of Microglia-mediated Neuroinflammation

Abstract

Nanomedicine, an emerging therapeutic tool in current medical frontiers, offers targeted drug delivery for many neurodegenerative disorders. Neuroinflammation, a hallmark of many neurodegenerative disorders, is mediated by microglia, the resident immunocompetent cells of the central nervous system (CNS). Microglial cells respond to various stimuli in the CNS resulting in their activation which may have a beneficial or a detrimental effect. In general, the activated microglia remove damaged neurons and infectious agents by phagocytosis, therefore being neuroprotective. However, their chronic activation exacerbates neuronal damage through excessive release of proinflammatory cytokines, chemokines and other inflammatory mediators which contribute to neuroinflammation and subsequent neurodegeneration in the CNS. Hence, controlling microglial inflammatory response and their proliferation has been considered as an important aspect in treating neurodegenerative disorders. Regulatory factors that control microglial activation and proliferation also play an important role in microglia-mediated neuroinflammation and neurotoxicity. Various anti-inflammatory drugs and herbal compounds have been identified in treating microglia-mediated neuroinflammation in the CNS. However, hurdles in crossing blood brain barrier (BBB), expression of metabolic enzymes, presence of efflux pumps and several other factors prevent the entry of these drugs into the CNS. Use of non-degradable delivery systems and microglial activation in response to the drug delivery system further complicate drug delivery to the CNS. Nanomedicine, a nanoparticle-mediated drug delivery system, exhibits immense potential to overcome these hurdles in drug delivery to the CNS enabling new alternatives with significant promises in revolutionising the field of neurodegenerative disease therapy. This review attempts to summarise various regulatory factors in microglia, existing therapeutic strategies in controlling microglial activation, and how nanotechnology can serve to improve the delivery of therapeutic drugs across the BBB for treating microglia- mediated neuroinflammation and neurodegeneration.

Microglia Increase Inflammatory Responses in iPSC-Derived Human BrainSpheres

“…As microglia occupy a central position in the defense and maintenance of the CNS, a 3D in vitro model including microglia could be fundamental for studies of the brain. Moreover, various anti-inflammatory drugs have been identified in treating microglia-mediated neuroinflammation in the CNS (Baby et al, 2014). The proposed model could serve as a potential tool for the screening of therapeutic targets in neurological disorders and recovery from brain injury.…”

Retinal Microglia in Glaucoma

“…Various strategies and models for inhibiting activated microglial cells have therefore been developed. 72 As an overactivation of retinal microglia is detrimental to the retinal ganglion cells in glaucomatous optic neuropathy, one may postulate that inhibition of activated retinal microglial cells may play a role in the treatment of the glaucoma. The retinal microglial cells may be inhibited pharmacologically.…”

Synthesis of gold and silver nanoparticles using flavonoid quercetin and their effects on lipopolysaccharide induced inflammatory response in microglial cells

“…The existing microglial activation damage of neurons through these proinflammatory products at minimum causes an increase in neuron death (Heneka et al 2014;Marín-Teva et al 2010). Therapeutic approaches with the use of bioflavonoids to alleviate LPS-induced proinflammatory gene activation underscore the important role of these compounds as potential therapeutic targets to ameliorate neuro-inflammatory neurodegenerative diseases (Choi et al 2011;Baby et al 2014).…”