The Blood brain barrier (BBB) is a tight junction which comprise of endothelial cells, astrocytes, pericytes and vascular basement membrane. It plays vital role in optimal CNS physiology, prevents passage of large-molecule drugs and partially prevents (upto 98%) passage of small bioactive molecules. Modern medicine has afforded us new drugs that could successfully treat various disease pathologies but were found ineffective due to their inability to cross the BBB. Deformable nanovesicles (DNV) are liposomes that can change shape due to presence of surfactants.  Our Tf-DNVs represent a brain targeted drug delivery system that has the potential to expand the therapeutic landscape of drug molecules that could be used in the treatment of CNS disorders. Using a microfluidic reactor we demonstrate that these Tf-DNVs can be produced in good yield with high encapsulation efficiency, and these vesicles have good long term stability. In the present investigations, we report the conjugation, isolation and characterization of a phospholipid to transferrin. This conjugated phospholipid is then used as needed in the microfluidic synthesis of the DNVs with the liposome surface modified with transferrin and encapsulating the bioflavanoid galangin (Gal) that has been reported as an amyloid precursor protein (APP) specific β-secretase inhibitor. The Tf-DNVs were tested in the Caco-2 permeability assay to demonstrate enhanced permeability. The proof-of-concept testing to be shown in an Alzheimer’s disease (AD) mouse model. Furthermore, these DNVs have the potential for transdermal delivery of Gal and other low brain permeability drugs into the brain. Microfluidics based approach allows the convenient and continuous synthesis of unilamellar nanovesicles in a manner that is also rapid, tunable for size,  and scalable- making it suitable for pharmaceutical development and clinical translation.<br/> <br/>

Brain targeting transferrin conjugated deformable nanovesicle (Tf-DNV) encapsulating the bioflavonoid galangin: A nanocarrier prepared by an adaptable microfluidic platform

253rd National Meeting (2017)

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