Nanoparticle Surface Charges Alter Blood–Brain Barrier Integrity and Permeability

Lockman, Paul R.; Koziara, Joanna M.; Mumper, Russell J.; Allen, David

doi:10.1080/10611860400015936

Cited by 633 publications

(336 citation statements)

References 29 publications

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“…However, the nonspecific nature of absorptive-mediated transport greatly limits its therapeutic potential, as indiscriminate cellular uptake is not only a major disadvantage in terms of off-target effects, but also for their reduced pharmacokinetic properties. Additionally, cationic compounds have been shown to cause acute toxicity and disruption of BBB permeability in vivo, which further brings into question the utility of altering surfaces charges as a means of increasing brain uptake [100].…”

Section: Endogenous Transport Systems As a Means To Enhance Antibody mentioning

confidence: 99%

Developing Therapeutic Antibodies for Neurodegenerative Disease

Yu¹,

Watts²

2013

Neurotherapeutics

176

171

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The central nervous system has been considered off-limits to antibody therapeutics. However, recent advances in preclinical and clinical drug development suggest that antibodies can cross the blood-brain barrier in limited quantities and act centrally to mediate their effects. In particular, immunotherapy for Alzheimer's disease has shown that targeting beta amyloid with antibodies can reduce pathology in both mouse models and the human brain, with strong evidence supporting a central mechanism of action. These findings have fueled substantial efforts to raise antibodies against other central nervous system targets, particularly neurodegenerative targets, such as tau, beta-secretase, and alpha-synuclein. Nevertheless, it is also apparent that antibody penetration across the blood-brain barrier is limited, with an estimated 0.1-0.2 % of circulating antibodies found in brain at steady-state concentrations. Thus, technologies designed to improve antibody uptake in brain are receiving increased attention and are likely going to represent the future of antibody therapy for neurologic diseases, if proven safe and effective. Herein we review briefly the progress and limitations of traditional antibody drug development for neurodegenerative diseases, with a focus on passive immunotherapy. We also take a more in-depth look at new technologies for improved delivery of antibodies to the brain.

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Section: Endogenous Transport Systems As a Means To Enhance Antibody mentioning

confidence: 99%

Developing Therapeutic Antibodies for Neurodegenerative Disease

Yu¹,

Watts²

2013

Neurotherapeutics

176

171

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“…The binding of Tf on the surface of PLA NPs was confirmed by XPS and zeta-potentials analysis. The zetapotentials of the NPs are negative, which is very important for obtaining low toxicity towards BBB (42). The characterization above demonstrated that the nanoscale drug delivery system with the targeting and transmembrane functions, Tf-PLA, was successfully constructed.…”

Section: Discussionmentioning

confidence: 98%

Inhibition of C6 glioma in vivo by combination chemotherapy of implantation of polymer wafer and intracarotid perfusion of transferrin-decorated nanoparticles

Han

Ren²,

Long³

et al. 2011

Oncol Rep

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Abstract. The objective of this study was to develop a combination chemotherapy of implantation of a 3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-loaded wafer and intracarotid perfusion of BCNU-loaded nanoparticles for glioma treatment in vivo. BCNU-loaded poly(D,L-lactic acid) (PLA) nanoparticles coated with transferrin (Tf) were prepared by a solvent evaporation/diffusion method using Tf as the emulsifier. X-ray photoelectron spectroscopy, BrattonMarshall colorimetric assay and zeta-potential analysis confirmed the existence of Tf on the nanoparticles and their functional activities. BCNU-loaded PLA wafers were made of BCNU-loaded PLA microspheres. In vitro drug release behavior demonstrated that BCNU was released from the Tf-PLA nanoparticles and wafers in two distinct phases. The biodistribution of Tf-coated nanoparticles investigated by 99m Tc-labeled single-photon emission computed tomography (SPECT) showed that the surface-containing Tf-PLA nanoparticles were concentrated in the brain. Inhibition of tumor growth in the C6 glioma-bearing animal model showed that combinational chemotherapy of BCNU-loaded wafer and BCNU-loaded PLA nanoparticles had a stronger inhibitory effect and prolonged the average survival time of rats (164%) compared with that of the control group. Furthermore, the tumors of this treatment group were not visible by examination at 4 weeks. The results of this study demonstrate for the first time that combination therapy of implantation of a BCNUloaded wafer and intracarotid perfusion of BCNU-loaded nanoparticles may be a new strategy for glioma gene therapy.

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“…As a result, a coherent profile of NMs health hazards begin to emerge, demonstrating that reactive oxygen species 12 , oxidative stress 13 and modified inflammatory responses 14 play important roles in their animal and cellular toxicity. The results of the above projects also show relationships among key physico-chemical characteristics, modes of action and biological responses, indicating that factors such as surface area and reactivity 15 , surface charge 16 , solubility, shape 17 and chemical composition are all key. However, our understanding of the long term effects of MNs is at an early stage, especially for MNs released from real products and for environmental species.…”

Section: Introductionmentioning

confidence: 99%

SUN: Paving Sustainable Nanoinnovation

Marcomini¹,

Hristozov²,

Jensen³

et al. 2014

Proceedings of the 4th World Sustainability Forum

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Our understanding of the environmental, health and safety (EHS) risks from nanotechnologies is still limited, which may result in over-balancing regulations and demolished consumer confidence. SUN is based on the hypothesis that the current knowledge on environmental and health risks of nanomaterials, whilst limited, can nevertheless guide nanomanufacturing to avoid future liabilities, provided that an integrated approach that addresses the complete product lifecycle of production, use and disposal is applied. This approach aims to give clear answers to questions from regulatory authorities, and open new possibilities for innovators to design greener nanotechnologies through development and application of new methods and tools for prediction of long-term exposure, OPEN ACCESS 2 effects and risks for humans and ecosystems (services), practices for risk prevention and management and tools to streamline effective decision making about safer products and processes.

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Nanoparticle Surface Charges Alter Blood–Brain Barrier Integrity and Permeability

Abstract: (1) Neutral NPs and low concentration anionic NPs can be utilized as colloidal drug carriers to brain, (2) cationic NPs have an immediate toxic effect at the BBB and (3) NP surface charges must be considered for toxicity and brain distribution profiles.

Cited by 633 publications

References 29 publications

Developing Therapeutic Antibodies for Neurodegenerative Disease

Developing Therapeutic Antibodies for Neurodegenerative Disease

Inhibition of C6 glioma in vivo by combination chemotherapy of implantation of polymer wafer and intracarotid perfusion of transferrin-decorated nanoparticles

SUN: Paving Sustainable Nanoinnovation

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