Abstract
Sustained and safe delivery of therapeutic agents across the blood–brain barrier (BBB) is one of the major challenges for the treatment of neurological disorders as this barrier limits the ability of most drug molecules to reach the brain. Targeted delivery of the drugs used to treat these disorders could potentially offer a considerable reduction of the common side effects of their treatment. The preparation and characterization of carboxymethyl cellulose (CMC) coated magnetic nanoparticles (Fe3O4@CMC) is reported as an alternative that meets the need for novel therapies capable of crossing the BBB. In vitro assays were used to evaluate the ability of these polysaccharide coated biocompatible, water-soluble, magnetic nanoparticles to deliver drug therapy across a model of the BBB. As a drug model, dopamine hydrochloride loading and release profiles in physiological solution were determined using UV-Vis spectroscopy. Cell viability tests in Human Lung Microvascular Endothelial (HLMVE) cell cultures showed no significant cell death, morphological changes or alterations in mitochondrial function after 24 and 48 h of exposure to the nanoparticles. Evidence of nanoparticle interactions and nanoparticle uptake by the cell membrane was obtained by electron microscopy (SEM and TEM) analyses. Permeability through a BBB model (the transwell assay) was evaluated to assess the ability of Fe3O4@CMC nanoparticles to be transported across a densely packed HLMVE cell barrier. The results suggest that these nanoparticles can be useful drug transport and release systems for the design of novel pharmaceutical agents for brain therapy.
Highlights
Neurodegenerative disorders such as Parkinson's and Alzheimer's diseases are the leading cause of disability and the second cause of mortality worldwide; these disorders affect more than 250 million people globally
Nanoparticles of magnetite, Fe3O4, and silanized magnetite, Si–Fe3O4, were synthesized as superparamagnetic carrier cores through the chemical coprecipitation method.[56,61]. These magnetic nanoparticles were coated with the polysaccharide carboxymethyl cellulose (CMC) by an electrostatic adsorption method.[62]
The hydrodynamic radii were similar in both cases, and the aqueous suspensions were stable for several days at room temperature, which agrees with their highly negative zeta potential values
Summary
While brain-targeted drug delivery has been gaining increasing attention, these strategies pose a signi cant challenge for drug developers. Magnetite (Fe3O4) SPIONs have received widespread acceptance within the scienti c community as their magnetic properties make them highly attractive for biomedical applications, especially as agents for MRI and targeted drug delivery.[9,10] The biocompatibility of these particles is frequently enhanced with organic or inorganic coatings that allow their suspension in aqueous or organic media.[11] A er drug molecules are attached to these delivery systems, the biodegradability, pH, ion and/or temperature sensibility of the materials can be used to activate drug delivery at a controlled and sustained rate to the target areas of the brain.[12] An advantage of biopolymer-coated magnetic nanoparticles is that they have shown lower toxicity levels compared to those with bare cores.
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