Dendrimeric Poly(Epsilon-Lysine) Delivery Systems for the Enhanced Permeability of Flurbiprofen across the Blood-Brain Barrier in Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive brain disorder and age-related disease
characterised by abnormal accumulation of -amyloid (A). The development of drugs to combat AD
is hampered by the lack of therapeutically-active molecules able to cross the blood-brain barrier (BBB).
It is agreed that specifically-designed carriers, such as dendrimers, could support the drug penetration
across the BBB. The aim of this study was to design biocompatible and biodegradable dendrimeric
delivery systems able to carry Flurbiprofen (FP), as drug for AD treatment, across the BBB and
liberate it at the target tissue. These dendrons were synthesised using solid-phase peptide synthesis
method and characterised by mass spectrometry and fourier-transform infrared spectroscopy (FTIR).
The results revealed successful synthesis of dendrons having FP been integrated during the synthesis
at their branching ends. Cytotoxicity assays demonstrated the biocompatibility of the delivery
systems, whereas HPLC analysis showed high percentages of permeability across an in vitro BBB
model for FP-integrated dendrons. Results also revealed the efficiency of drug conjugates on the secretase enzyme in target cells with evidence of eventual drug release by hydrolysis of the carrier.
This study demonstrates that the coupling of FP to dendrimeric delivery systems can successfully be
achieved during the synthesis of the poly(epsilon-lysine) macromolecules to improve the transport of
the active drug across the BBB.