Abstract
Magnetic nanoparticles have great prospects for drug delivery purposes, as they can be designed with various surface coatings and conjugated with drugs and targeting moieties. They also have a unique potential for precise delivery when guided by magnetic force. The blood-brain barrier (BBB) denotes the interface between the blood and brain parenchyma and hinders the majority of drugs from entering the brain. Red fluorescent magnetic nanoparticles were encapsulated in liposomes and conjugated to antibodies targeting the rat transferrin receptor (OX26) to form magnetic immunoliposomes. These magnetic immunoliposomes enhanced the uptake by rat brain capillary endothelial cells (BCECs) in vitro. In situ brain perfusion in young rats high in the endogenous expression of transferrin receptors by BCECs, revealed enhanced uptake of magnetic immunoliposomes when compared to naked magnetic nanoparticles or non-targeted magnetic liposomes. When applying the external magnetic force, the magnetic nanoparticles were detected in the brain parenchyma, suggesting transport across the BBB. Ultrastructural examination of the immunoliposomes, unfortunately, was unable to confirm a complete encapsulation of all naked nanoparticles within the liposomes, suggesting that the data on the brain could derive from particles being released from the liposomes under influence of external magnetic force; hence hypothesizes on external magnetic force as a qualifier for dragging targeted magnetic immunoliposomes through the BBB. In conclusion, our results suggest that transport of magnetic nanoparticles present in BCECs by targeted delivery to the transferrin receptor may undergo further transport into the brain when applying magnetic force. While magnetic immunoliposomes are targetable to BCECs, their design to enable further transport across the BBB when applying external magnetic force needs further improvement.
Highlights
Nanotechnology enables the design of nanoparticles for numerous medical purposes; e.g., liposomes at the nanoscale are amenable for therapy in treatment of cancer and chronic diseases affecting the nervous system [1,2,3]
The in vitro uptake studies proved that embedding magnetic nanoparticles into a cationic lipid bilayer led to a 4.5 fold increase in fluorescence intensity within the RBE4 cells, which is consistent with bilayer led to a 4.5 fold increase in fluorescence intensity within the RBE4 cells, which is consistent prior observations of facilitated uptake of cationic liposomes in endothelial cells [36]
The uptake of magnetic liposomes compared to magnetic nanoparticles was probably due to favorable increased uptake of magnetic liposomes compared to magnetic nanoparticles was probably due to favorable interactions of cationic liposomes with the cell membrane and subsequent uptake by adsorptive endocytosis [27,36,45]
Summary
Nanotechnology enables the design of nanoparticles for numerous medical purposes; e.g., liposomes at the nanoscale are amenable for therapy in treatment of cancer and chronic diseases affecting the nervous system [1,2,3]. The magnetic liposomes consisting of liposomes shielding magnetic nanoparticles in a lipid bilayer, denote a new drug carrier that allows the magnetic guidance of nanoparticles by an external magnet. These liposomes can be designed to contain polyethylene. Materials 2019, 12, 3576 glycol (PEG)-conjugated phospholipids (PEGylated phospholipids) to increase the plasma half-life [4,5]. These PEGylated phospholipids can be functionalized by conjugating a targeting ligand or antibody [4,5,6,7]. The use of magnetic liposomes may carry the potential for such a purpose by means of antibody-targeting to these endogenous molecules [12]
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