Abstract
Earlier studies proved the success of using chemically functionalised multi-walled carbon nanotubes (f-MWNTs) as nanocarriers to the brain. Little insight into the kinetics of brain distribution of f-MWNTs in vivo has been reported. This study employed a wide range of qualitative and quantitative techniques with the aim of shedding the light on f-MWNT's brain distribution following intravenous injection. γ-Scintigraphy quantified the uptake of studied radiolabelled f-MWNT in the whole brain parenchyma and capillaries while 3D-single photon emission computed tomography/computed tomography imaging and autoradiography illustrated spatial distribution within various brain regions. Raman and multiphoton luminescence together with transmission electron microscopy confirmed the presence of intact f-MWNT in mouse brain, in a label-free manner. The results evidenced the presence of f-MWNT in mice brain parenchyma, in addition to brain endothelium. Such information on the rate and extent of regional and cellular brain distribution is needed before further implementation into neurological therapeutics can be made.
Highlights
Drug transfer to the brain is greatly limited at the blood–brain barrier (BBB) by highly restrictive tight junctions between capillary endothelial cells [1]
MWNT-Fab′ functionalised with DTPA was radiolabelled with 111In to yield [111In]MWNT-Fab′ and 49.4 ± 5.4% labelling efficiency was achieved as assessed by TLC examination (Fig. S2)
The kinetic distribution of 111In-labelled MWNT-Fab′-DTPA within the brain environment was investigated in this study by quantitative γ-scintigraphy, SPECT/CT imaging and autoradiography after i.v. injection in mice
Summary
Drug transfer to the brain is greatly limited at the blood–brain barrier (BBB) by highly restrictive tight junctions between capillary endothelial cells [1]. Improvements in drug transport across the BBB have been shown by directly altering the physicochemical properties of the drug, or coupling drugs to a vector including peptides, antibodies or nanoparticles (NPs) [2,3] which are transported across the BBB by endogenous receptor- or adsorptive-mediated transcytotic pathways. The maturation of nanotechnology applications in biomedicine means that NPs with high drug payloads can be engineered to have physiochemical properties (K.T. Al-Jamal). They can be surface functionalised with biological ligands to target or cross the BBB
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