Evaluation of Targeted Delivery to the Brain Using Magnetic Immunoliposomes and Magnetic Force

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.

Focused Ultrasound and Microbubble Treatment Increases Delivery of Transferrin Receptor-Targeting Liposomes to the Brain

“…Here we used liposomes functionalized with OX26, a well-known antibody against the rat TfR, which does not compete with endogenous transferrin (Pardridge 2015). In previous work, the OX26 antibody has shown good specificity toward the rat TfR both in vitro and in vivo, and liposomes conjugated with the OX26 antibody have shown good targeting ability toward the brain microvasculature in post-natal rats (Johnsen et al 2017;Thomsen et al 2019). In the present work, we have combined intravenous injection of Anti-TfR liposomes with FUS-induced increase of BBB permeability to investigate if this approach enhanced the delivery of the Anti-TfR liposomes across the BBB compared with liposomes lacking the targeting moiety.…”

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

“…In particular, brain tumor targeting is one of their most common applications mainly due to the ease of recognition by cancer cells as well [ 184 ]. Although targeting of TFR has been achieved with the aid of antibodies such as OX26 [ 218 ] and RI7-217 [ 217 ], they have shown different affinities within animal models (e.g., rats vs. mice) [ 234 ]. Similarly, antibodies have been employed for targeting the insulin growth factor receptor (IGFR), which is also highly expressed in the BBB and taken up by CME [ 235 ].…”

The Paradox of HIV Blood–Brain Barrier Penetrance and Antiretroviral Drug Delivery Deficiencies

“…Similar macrophage uptake has been observed in a long-acting dolutegravir prodrug encapsulated in a poloxamer nanoformulation [ 88 ]. To enhance transmigration across the BBB, nanoparticles utilizing a ferrous magnet-based liposome nanocarrier resulted in a 7.3-fold increase of transmigration with the synergistic support from transferrin receptors on the epithelium in vitro without affecting BBB integrity [ 92 ]. Similarly, the discovery of magnetic azidothymidine 5′-triphosphate (AZTTP) liposome demonstrated a threefold increase in migrating across the BBB compared with free AZTTP by utilizing the guidance of an external magnetic field to deliver the nanoparticle to a specific site of interest [ 93 ].…”