title: Enhanced blood-brain barrier transmigration using a novel transferrin embedded fluorescent magneto-liposome nanoformulation.
abstract: The blood-brain barrier (BBB) is considered as the primary impediment barrier for most drugs. Delivering therapeutic agents to the brain is still a big challenge to date. In our study, a dual mechanism, receptor mediation combined with external non-invasive magnetic force, was incorporated into ferrous magnet-based liposomes for BBB transmigration enhancement. The homogenous magnetic nanoparticles (MNPs), with a size of ∼10 nm, were synthesized and confirmed by TEM and XRD respectively. The classical magnetism assay showed the presence of the characteristic superparamagnetic property. These MNPs encapsulated in PEGylated fluorescent liposomes as magneto-liposomes (MLs) showed mono-dispersion, ∼130 ± 10 nm diameter, by dynamic laser scattering (DLS) using the lipid-extrusion technique. Remarkably, a magnetite encapsulation efficiency of nearly 60% was achieved. Moreover, the luminescence and hydrodynamic size of the MLs was stable for over two months at 4 ° C. Additionally, the integrity of the ML structure remained unaffected through 120 rounds of circulation mimicking human blood fluid. After biocompatibility confirmation by cytotoxicity evaluation, these fluorescent MLs were further embedded with transferrin and applied to an in vitro BBB transmigration study in the presence or absence of external magnetic force. Comparing with magnetic force- or transferrin receptor-mediated transportation alone, their synergy resulted in 50-100% increased transmigration without affecting the BBB integrity. Consequently, confocal microscopy and iron concentration in BBB-composed cells further confirmed the higher cellular uptake of ML particles due to the synergic effect. Thus, our multifunctional liposomal magnetic nanocarriers possess great potential in particle transmigration across the BBB and may have a bright future in drug delivery to the brain.
authors.affiliation: Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA. Institute of NeuroImmune Pharmacology, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.forename: Vidya
authors.initials: V
authors.lastname: Sagar
authors.forename: Marisela
authors.initials: M
authors.lastname: Agudelo
authors.forename: Sudheesh
authors.initials: S
authors.lastname: Pilakka-Kanthikeel
authors.forename: Venkata Subba Rao
authors.initials: VS
authors.lastname: Atluri
authors.forename: Andrea
authors.initials: A
authors.lastname: Raymond
authors.forename: Thangavel
authors.initials: T
authors.lastname: Samikkannu
authors.forename: Madhavan P
authors.initials: MP
authors.lastname: Nair
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D008280:Magnetics; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000633:toxicity / Q000648:ultrastructure; D008954:Models, Biological; D036103:Nanotechnology; D010316:Particle Size; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000008:administration & dosage
chemical_list: D005456:Fluorescent Dyes; D008081:Liposomes; D058185:Magnetite Nanoparticles; D011990:Receptors, Transferrin; D014168:Transferrin