Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain

Abstract

Nanoparticles made of human serum albumin (HSA) and modified with apolipoproteins have previously been shown to transport drugs, which normally do not enter the brain, across the blood-brain barrier (BBB). However the precise mechanism by which nanoparticles with different apolipoproteins on their surface can target to the brain, as yet, has not been totally elucidated. In the present study, HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A-I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats. The rodents were sacrificed after 15 or 30 min, and their brains were examined by transmission electron microscopy. Apo A-I nanoparticles could be found inside the endothelial cells of brain capillaries as well as within parenchymal brain tissue of both, mice and rats, whereas control particles without Apo A-I on their surface did not cross the BBB during our experiments. The maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated by perfusion with a fixative containing lanthanum nitrate as an electron dense marker for the permeability of tight junctions.

Keywords::

• Apolipoprotein
• blood-brain barrier
• brain targeting
• electron microscopy
• endothelial cell
• human serum albumin
• nanoparticles
• mice
• rats
• tight junctions

Acknowledgements

The authors would like to thank Susann Münzner for the technical support during the electron microscopy studies as well as Dr. Alice Warley and Ken Brady of the Centre for Ultrastructural Imaging at King’s College London for preparation of the specimens for electron microscopy.

Declaration of interest

The authors report no declarations of interests.