Surfactants influence polymer nanoparticle fate within the brain

Joseph, Andrea; Simo, Georges Motchoffo; Gao, Torahito A; Alhindi, Norah; Xu, Nuo; Graham, Daniel J.; Gamble, Lara J.; Nance, Elizabeth

doi:10.1016/j.biomaterials.2021.121086

Cited by 34 publications

(24 citation statements)

References 48 publications

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“…We leveraged MPT, a technique that has been used in combination with brain slices of multiple different species [ 49 , 76 , 77 ], to provide a measure of local extracellular microenvironment changes in normal culturing conditions and in response to OGD. Most existing applications of MPT in brain tissue have focused on altering nanoparticle physicochemical properties to optimize drug delivery properties [ 49 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

Organotypic whole hemisphere brain slice models to study the effects of donor age and oxygen-glucose-deprivation on the extracellular properties of cortical and striatal tissue

et al. 2022

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Background The brain extracellular environment is involved in many critical processes associated with neurodevelopment, neural function, and repair following injury. Organization of the extracellular matrix and properties of the extracellular space vary throughout development and across different brain regions, motivating the need for platforms that provide access to multiple brain regions at different stages of development. We demonstrate the utility of organotypic whole hemisphere brain slices as a platform to probe regional and developmental changes in the brain extracellular environment. We also leverage whole hemisphere brain slices to characterize the impact of cerebral ischemia on different regions of brain tissue. Results Whole hemisphere brain slices taken from postnatal (P) day 10 and P17 rats retained viable, metabolically active cells through 14 days in vitro (DIV). Oxygen-glucose-deprivation (OGD), used to model a cerebral ischemic event in vivo, resulted in reduced slice metabolic activity and elevated cell death, regardless of slice age. Slices from P10 and P17 brains showed an oligodendrocyte and microglia-driven proliferative response after OGD exposure, higher than the proliferative response seen in DIV-matched normal control slices. Multiple particle tracking in oxygen-glucose-deprived brain slices revealed that oxygen-glucose-deprivation impacts the extracellular environment of brain tissue differently depending on brain age and brain region. In most instances, the extracellular space was most difficult to navigate immediately following insult, then gradually provided less hindrance to extracellular nanoparticle diffusion as time progressed. However, changes in diffusion were not universal across all brain regions and ages. Conclusions We demonstrate whole hemisphere brain slices from P10 and P17 rats can be cultured up to two weeks in vitro. These brain slices provide a viable platform for studying both normal physiological processes and injury associated mechanisms with control over brain age and region. Ex vivo OGD impacted cortical and striatal brain tissue differently, aligning with preexisting data generated in in vivo models. These data motivate the need to account for both brain region and age when investigating mechanisms of injury and designing potential therapies for cerebral ischemia.

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Section: Discussionmentioning

confidence: 99%

Organotypic whole hemisphere brain slice models to study the effects of donor age and oxygen-glucose-deprivation on the extracellular properties of cortical and striatal tissue

et al. 2022

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“…There is no yet clear experimental evidence of anomalous diffusion in the brain’s ECS (in contrast to intracellular transport and transport of water molecules [ 45 , 72 , 73 ]), although some primary recent observations can be noted, e.g., [ 74 ]. For this reason, we simply refer to some classic reviews of anomalous diffusion considered from the random walk point of view [ 75 , 76 ], including the special attention to the processes, which occur in complex (including labyrinthine) environments [ 77 ], without the detailed consideration of such mechanisms.…”

Section: Physics Of Diffusion: What Can Be Searched For In Brain’s Ecs?mentioning

confidence: 99%

Transport in the Brain Extracellular Space: Diffusion, but Which Kind?

Postnikov

Lavrova

Postnov

2022

IJMS

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The mechanisms of transport of substances in the brain parenchyma have been a hot topic in scientific discussion in the past decade. This discussion was triggered by the proposed glymphatic hypothesis, which assumes a directed flow of cerebral fluid within the parenchyma, in contrast to the previous notion that diffusion is the main mechanism. However, when discussing the issue of “diffusion or non-diffusion”, much less attention was given to the question that diffusion itself can have a different character. In our opinion, some of the recently published results do not fit into the traditional understanding of diffusion. In this regard, we outline the relevant new theoretical approaches on transport processes in complex random media such as concepts of diffusive diffusivity and time-dependent homogenization, which expands the understanding of the forms of transport of substances based on diffusion.

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“…NPs can be used to help BBB-crossing drug delivery in a relatively mild way . Apart from the general advantages about the flexibility in surface modification and controllability to load and release drugs, , NPs are able to target microglia due to the intrinsic capability of microglia to internalize foreign bodies. , The microglial targeting extent of NPs can be modulated by their dimension and surface charge as well . Dendrimer-based NPs are promising in neuroinflammation-targeting, especially poly (amidoamine) (PAMAM) dendrimers, which have a well-defined size (3–12 nm) and a profoundly precise molecular structure with a multivalent surface, and can cross the impaired BBB without any targeting ligand .…”

Section: Delivery Strategies Reinforced Efficient Microglial Manipula...mentioning

confidence: 99%

Advanced Therapies for Traumatic Central Nervous System Injury: Delivery Strategy Reinforced Efficient Microglial Manipulation

Huang

2022

Mol. Pharmaceutics

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Traumatic central nervous system (CNS) injuries, including spinal cord injury and traumatic brain injury, are challenging enemies of human health. Microglia, the main component of the innate immune system in CNS, can be activated postinjury and are key participants in the pathological procedure and development of CNS trauma. Activated microglia can be typically classified into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. Reducing M1 polarization while promoting M2 polarization is thought to be promising for CNS injury treatment. However, obstacles such as the low permeability of the blood–brain barrier and short retention time in circulation limit the therapeutic outcomes of administrated drugs, and rational delivery strategies are necessary for efficient microglial regulation. To this end, proper administration methods and delivery systems like nano/microcarriers and scaffolds are investigated to augment the therapeutic effects of drugs, while some of these delivery systems have self-efficacies in microglial manipulation. Besides, systems based on cell and cell-derived exosomes also show impressive effects, and some underlying targeting mechanisms of these delivery systems have been discovered. In this review, we introduce the roles of microglia play in traumatic CNS injuries, discuss the potential targets for the polarization regulation of microglial phenotype, and summarize recent studies and clinical trials about delivery strategies on enhancing the effect of microglial regulation and therapeutic outcome, as well as targeting mechanisms post CNS trauma.

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Surfactants influence polymer nanoparticle fate within the brain

Cited by 34 publications

References 48 publications

Organotypic whole hemisphere brain slice models to study the effects of donor age and oxygen-glucose-deprivation on the extracellular properties of cortical and striatal tissue

Organotypic whole hemisphere brain slice models to study the effects of donor age and oxygen-glucose-deprivation on the extracellular properties of cortical and striatal tissue

Transport in the Brain Extracellular Space: Diffusion, but Which Kind?

Advanced Therapies for Traumatic Central Nervous System Injury: Delivery Strategy Reinforced Efficient Microglial Manipulation

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