Image-guided drug delivery to the brain using nanotechnology

Abstract

Targeting across the blood-brain barrier (BBB) for treatment of central nervous system (CNS) diseases represents the most challenging aspect of, as well as one of the largest growing fields in, neuropharmaceutics. Combining nanotechnology with multiple imaging techniques has a unique role in the diagnosis and treatment (theranostics) of CNS disease. Such imaging techniques include anatomical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound (US), X-ray computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT), electron microscopy, autoradiography and optical imaging as well as thermal images. In this review, we summarize and discuss recent advances in formulations, current challenges and possible hypotheses concerning the use of such theranostics across the BBB.

Figure 1

[LM18]A cerebral capillary enclosed in astrocyte end-feet. Characteristics of the blood-brain barrier (BBB) are indicated: (a) tight junctions (TJs) that seal the pathway between the capillary (endothelial) cells; (b) the lipid nature of the cell membranes of the capillary wall makes it a barrier to water-soluble molecules; (c–e) represent some of the carriers and ion channels in the BBB; (f) the ‘enzymatic barrier’ that removes molecules from the blood; (g) the efflux pumps that extrude fat-soluble molecules that have crossed into the cells.

Figure 2

[LM19]Potential transport mechanisms across the blood–brain barrier (BBB). Diffusion and active transport are the main transport mechanisms.

Figure 3

Magnetic resonance image-guided focused ultrasound (MRIgFUS) drug delivery across the blood–brain barrier (BBB) using polymer-coated magnetic nanoparticles (MNPs) conjugated with epirubicin. (a) Intact central nervous system (CNS) capillaries. (b) Disruption of the BBB through activation of microbubbles (MBs) by FUS, enhancing the passive influx of therapeutic MNPs. (c) Active delivery of therapeutic MNPs to the brain through the use of combined magnetic targeting (MT) with FUS. (d) In vivo imaging of MNP distribution in the brain using FUS alone. (e) In vivo imaging of the distribution of MNPs in the brain using FUS and MT 6 h post treatment. Abbreviations: A, astrocyte; EC, endothelial cell; N, neuron; P, pericyte. Reproduced, with permission, from [27].