Nanomedicine in cerebral palsy

Balakrishnan, Bindu; Nance, Elizabeth; Johnston, Michael V.; Kannan, Rangaramanujam M.; Kannan, Sujatha

doi:10.2147/ijn.s35979

Cited by 15 publications

(13 citation statements)

References 133 publications

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“…In this in vivo study, we observed an increase dendrimer uptake with the progression of microglial activation. Specifically, microglial uptake at G31 (PND1) was greater than that of G29, likely due to the endotoxin-induced microglia activation that is more established at G31 than at G29 in this model [8,27,34]. …”

Section: Discussionmentioning

confidence: 99%

“…Pro-inflammatory activation of microglial cells can result in persistent neuroinflammation, including release of free radicals, excitotoxic metabolites, and pro-inflammatory cytokines, leading to diffuse white and grey matter injury at foci where conventional therapeutics cannot reach and achieve cellular-targeting [7]. Therefore, an effective therapeutic agent should cross the blood-brain barrier (BBB), achieve rapid transport to reach the cells associated with inflammation and injury, and should avoid uptake by healthy cells/regions of the brain [8–10]. …”

Section: Introductionmentioning

confidence: 99%

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Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers

Zhang

Nance

Zhi

et al. 2016

Journal of Controlled Release

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Cerebral Palsy (CP) is a chronic childhood disorder with limited therapeutic options. Maternal intrauterine inflammation/infection is a major risk factor in the pathogenesis of CP. In pre-clinical models, dendrimer-based therapies are viable in postnatal period, attenuating inflammation and improving motor function in vivo. However, treatment to the mother, in the prenatal period, may provide the possibility of preventing/resolving inflammation at early stages. Towards this goal, we used a maternal intrauterine inflammation-induced rabbit model of CP to study fetal-maternal transport and neuroinflammation targeting of intra-amniotically administrated dendrimers with neutral/anionic surface functionality. Our study suggested both hydroxyl-terminated ‘neutral’ (D-OH) and carboxyl-terminated ‘anionic’ (D-COOH) Polyamidoamine (PAMAM) dendrimers were absorbed by fetuses and demonstrated bi-directional transport between fetuses and mother. D-OH was more effective in crossing the fetal blood-brain barrier, and targeting activated microglia. The cell-specific targeting was associated with the extent of microglia activation. This study demonstrated intra-amniotically administered hydroxyl PAMAM dendrimers could be an effective drug delivery vehicle for targeting fetal inflammation and preventing subsequent neurologic injury associated with chorioamnionitis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers

Zhang

Nance

Zhi

et al. 2016

Journal of Controlled Release

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“…Nanoparticles, such as polyamidoamine dendrimers have been shown to concentrate in activated microglia and astrocytes in the brains of newborn rabbits with cerebral palsy, but not healthy controls. This nanotechnology approach has shown excellent results to deliver dendrimer-bound N -acetyl- l -cysteine (NAC) to microglia to suppress neuroinflammation, using much lower concentrations than are needed with systemic dosing ( 193 – 195 ).…”

Section: Anti-inflammatory and Immunomodulatory Therapies For Neuroprmentioning

confidence: 99%

Neuroinflammation and Neuroimmune Dysregulation after Acute Hypoxic-Ischemic Injury of Developing Brain

2015

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Hypoxic-ischemic (HI) injury to developing brain results from birth asphyxia in neonates and from cardiac arrest in infants and children. It is associated with varying degrees of neurologic sequelae, depending upon the severity and length of HI. Global HI triggers a series of cellular and biochemical pathways that lead to neuronal injury. One of the key cellular pathways of neuronal injury is inflammation. The inflammatory cascade comprises activation and migration of microglia – the so-called “brain macrophages,” infiltration of peripheral macrophages into the brain, and release of cytotoxic and proinflammatory cytokines. In this article, we review the inflammatory and immune mechanisms of secondary neuronal injury after global HI injury to developing brain. Specifically, we highlight the current literature on microglial activation in relation to neuronal injury, proinflammatory and anti-inflammatory/restorative pathways, the role of peripheral immune cells, and the potential use of immunomodulators as neuroprotective compounds.

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“…The first section conveys information on probably the best-known and most intensively studied biosimilar NMs applied in biotechnology and medicine such as liposomes, chitosan, and poly(lactic-co-glycolic acid) (PLGA) nanoparticles. These biocompatible and biodegradable NMs represent wide potential use in delivering a large variety of drugs and therapeutics including small molecules, herbal medicines, genes, proteins, miRNAs, and oligonucleotides ([ 30 , 31 ] and references cited; [ 9 , 14 , 22 , 25 , 32 – 34 ]). The focus of the second section is on the possibility to conclude on trait-nanotoxicity relationships.…”

Section: Emerging Consensusmentioning

confidence: 99%

“…Among polymeric NMs, that can encapsulate drug molecules and can be conjugated to targeting agents, dendrimers [ 11 , 19 , 31 , 35 – 38 ] are the preferred test materials, due to their versatile surface functions allowing a wide variety of chemical modifications of properties. By reflecting preclinical studies using NMs for the delivery of therapeutics designed for neuroinflammation and neurodegeneration such as Alzheimer's and Parkinson's diseases, multiple sclerosis or amyotrophic lateral sclerosis (ALS), cerebral palsy, ischemia/stroke, traumatic brain injury, and epilepsy ([ 31 ] and references cited), the third section concerns the growing realization of the unique biodistribution of NMs. It necessitates the development of new model systems providing parameters predictive for NM action in various disorders and pathophysiological conditions.…”

Section: Emerging Consensusmentioning

confidence: 99%

The Janus Facet of Nanomaterials

Kardos

Jemnitz

Jablonkai

et al. 2015

BioMed Research International

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Application of nanoscale materials (NMs) displays a rapidly increasing trend in electronics, optics, chemical catalysis, biotechnology, and medicine due to versatile nature of NMs and easily adjustable physical, physicochemical, and chemical properties. However, the increasing abundance of NMs also poses significant new and emerging health and environmental risks. Despite growing efforts, understanding toxicity of NMs does not seem to cope with the demand, because NMs usually act entirely different from those of conventional small molecule drugs. Currently, large-scale application of available safety assessment protocols, as well as their furthering through case-by-case practice, is advisable. We define a standard work-scheme for nanotoxicity evaluation of NMs, comprising thorough characterization of structural, physical, physicochemical, and chemical traits, followed by measuring biodistribution in live tissue and blood combined with investigation of organ-specific effects especially regarding the function of the brain and the liver. We propose a range of biochemical, cellular, and immunological processes to be explored in order to provide information on the early effects of NMs on some basic physiological functions and chemical defense mechanisms. Together, these contributions give an overview with important implications for the understanding of many aspects of nanotoxicity.

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Nanomedicine in cerebral palsy

Cited by 15 publications

References 133 publications

Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers

Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers

Neuroinflammation and Neuroimmune Dysregulation after Acute Hypoxic-Ischemic Injury of Developing Brain

The Janus Facet of Nanomaterials

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