rmp-7 and Alzheimer-Disease

A drug delivery system of quercetin (QU)-encapsulated liposomes (LS) grafted with RMP-7, a bradykinin analog, and lactoferrin (Lf) was developed to permeate the blood-brain barrier (BBB) and rescue degenerated neurons, acting as an Alzheimer's disease (AD) pharmacotherapy. This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS) was used to traverse human brain microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ) fibrils. We found that surface RMP-7 and Lf enhanced the ability of QU to cross the BBB without inducing strong toxicity and damaging the tight junction. In addition, RMP-7-Lf-QU-LS significantly reduced Aβ-induced neurotoxicity and improved the viability of SK-N-MC cells. Compared with free QU, RMP-7-Lf-QU-LS could also significantly inhibit the expression of phosphorylated c-Jun N terminal kinase, phosphorylated p38, and phosphorylated tau protein at serine 202 by SK-N-MC cells, indicating an important role of RMP-7, Lf, and LS in protecting neurons against apoptosis. RMP-7-Lf-QU-LS is a promising carrier targeting the BBB to prevent Aβ-insulted neurodegeneration and may have potential in managing AD in future clinical applications.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Apoptosis; Astrocytes; Blood-Brain Barrier; Bradykinin; Brain; Cell Line, Tumor; Cells, Cultured; Drug Delivery Systems; Endothelial Cells; Endothelium, Vascular; Humans; Lactoferrin; Liposomes; Neuroprotective Agents; Peptide Fragments; Quercetin

Liposomes with Cereport (RMP-7) and transferrin (Tf) (RMP-7/Tf/liposomes) were employed to target the blood-brain barrier (BBB) and to inhibit the degeneration of neurons insulted with fibrillar β-amyloid peptide 1-42 (Aβ1-42). Neuron growth factor (NGF)-encapsulated RMP-7/Tf/liposomes (RMP-7/Tf/NGF-liposomes) were used to permeate a monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to treat Aβ1-42 -attacked SK-N-MC cells. An increase in RMT-7 concentration increased the particle size, zeta potential, propidium iodide (PI) permeability, and NGF permeability, but decreased the cross-linking efficiency of RMT-7, viability of HBMECs and HAs, and transendothelial electrical resistance (TEER). In addition, an increase in Tf concentration enhanced the particle size, viability of HBMECs, HAs, and SK-N-MC cells, PI permeability, and NGF permeability, but reduced the zeta potential, cross-linking efficiency of RMT-7 and Tf, and TEER. RMP-7/Tf/NGF-liposomes can transport NGF across the BBB and improve the neuroprotection for Alzheimer's disease therapy in preclinical trials.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Astrocytes; Bradykinin; Brain; Cell Line; Cell Survival; Drug Delivery Systems; Endothelial Cells; Humans; Liposomes; Nerve Growth Factors; Neuroprotective Agents; Peptide Fragments; Transferrin