Rabies virus glycoprotein- and transferrin-functionalized liposomes to elevate epigallocatechin gallate and FK506 activity and mediate MAPK against neuronal apoptosis in Parkinson's disease

The difficulty of drugs to cross the blood-brain barrier (BBB) to reach specific sites and target multiple factors responsible for neurovegetative diseases necessitates the development of an effective drug delivery system. Rabies virus glycoprotein (RVG)- and transferrin (Tf)-grafted liposomes were constructed to deliver epigallocatechin gallate (EGCG) and FK506 to BBB against neurodegeneration for Parkinson's disease (PD) treatment. Surface RVG and Tf revealed substantial improvement in BBB permeability of EGCG and FK506, and incorporation of phosphatidy-l-serine (PS) in RVG-Tf-EGCG-FK506-liposomes ameliorated α-synuclein docking. EGCG and FK506-encapsulated liposomes decreased cytotoxicity to 1-methyl-4-phenylpyridinium-impacted neurons. Immunofluorescence and western blot studies demonstrated better activity of RVG-Tf-EGCG-FK506-PS-liposomes in suppressing Bax, α-synuclein, caspase-3, p-tau protein, p-p38, p-ERK1/2 and p-cJNK expressions, and in increasing Bcl-2, tyrosine hydroxylase, dopamine transporter, p-CREB and p-ERK5 expressions. Multi-targeted RVG-Tf-PS-liposomes advantaged BBB permeation and contributed to neuroprotective effect to promote the efficiency of EGCG and FK506 in PD management.