Recent Advances in the Therapeutic and Diagnostic Use of Liposomes and Carbon Nanomaterials in Ischemic Stroke

Abstract

The complexity of the central nervous system (CNS), its limited self-repairing capacity and the ineffective delivery of most CNS drugs to the brain contribute to the irreversible and progressive nature of many neurological diseases and also the severity of the outcome. Therefore, neurological disorders belong to the group of pathologies with the greatest need of new technologies for diagnostics and therapeutics. In this scenario, nanotechnology has emerged with innovative and promising biomaterials and tools. This review focuses on ischemic stroke, being one of the major causes of death and serious long-term disabilities worldwide, and the recent advances in the study of liposomes and carbon nanomaterials for therapeutic and diagnostic purposes. Ischemic stroke occurs when blood flow to the brain is insufficient to meet metabolic demand, leading to a cascade of physiopathological events in the CNS including local blood brain barrier (BBB) disruption. However, to date, the only treatment approved by the FDA for this pathology is based on the potentially toxic tissue plasminogen activator. The techniques currently available for diagnosis of stroke also lack sensitivity. Liposomes and carbon nanomaterials were selected for comparison in this review, because of their very distinct characteristics and ranges of applications. Liposomes represent a biomimetic system, with composition, structural organization and properties very similar to biological membranes. On the other hand, carbon nanomaterials, which are not naturally encountered in the human body, exhibit new modes of interaction with biological molecules and systems, resulting in unique pharmacological properties. In the last years, several neuroprotective agents have been evaluated under the encapsulated form in liposomes, in experimental models of stroke. Effective drug delivery to the brain and neuroprotection were achieved using stealth liposomes bearing targeting ligands onto their surface for brain endothelial cells and ischemic tissues receptors. Carbon nanomaterials including nanotubes, fullerenes and graphene, started to be investigated and potential applications for therapy, biosensing and imaging have been identified based on their antioxidant action, their intrinsic photoluminescence, their ability to cross the BBB, transitorily decrease the BBB paracellular tightness, carry oligonucleotides and cells and induce cell differentiation. The potential future developments in the field are finally discussed.

Keywords: carbon nanotubes; fullerenes; graphene; imaging; liposomes; nanobiosensor; nanocarrier; stroke.

FIGURE 1

Schematic representation of the brain tissue and the strategies used with liposomes or carbon nanomaterials to improve drug delivery into the ischemic regions (core and penumbra) following intravenous or intranasal route. The BBB is shown before and after an ischemic event.

FIGURE 2

Schematic representation of different liposome membrane functionalization strategies for application against ischemic stroke: PEGylation; cationic and/or anionic charges; and specific targeting ligands for BEC or ischemic tissue receptors.

FIGURE 3

Schematic representation of carbon-based nanomaterials that, due to their unique properties, have shown potential applications in the treatment and diagnosis of stroke: fullerene (hollow sphere of carbon atoms in sp² hybridization); carbon nanotube (tubular structure of carbon atoms in sp² hybridization); and graphene (single layer of carbon atoms arranged in a hexagonal lattice in sp² hybridization). Reprinted (adapted) with permission from Hong et al. (2015).

FIGURE 4

Schematic representation of surface functionalization and loading of carbon nanotubes for biomedical applications.