title: Grafting of cell-penetrating peptide to receptor-targeted liposomes improves their transfection efficiency and transport across blood-brain barrier model.
abstract: We report bifunctional liposomal delivery system, combining transferrin (Tf)-mediated receptor targeting and poly-L-arginine (PR)-facilitated cell penetration, which overcomes the drawback of saturation of delivery. PR was conjugated to the distal end of distearoyl phosphoethanolamine-polyethylene glycol (PEG) 2000 and was incorporated with other phospholipids in chloroform/methanol (2:1) to form PR liposomes using thin-film hydration technique. Tf-PEG phospholipid micelles were incorporated into PR liposomes using postinsertion technique to form Tf-PR liposomes. The bifunctional liposomes demonstrated significantly (p < 0.05) higher cellular uptake by brain endothelial cells (bEnd.3) and about eightfold higher transfection in primary culture of glial cells as compared with the Tf liposomes. Cell viabilities of Tf-conjugated and bifunctional liposomes were not markedly different; however, transport across in vitro blood-brain barrier model improved considerably after dual modification. The study underlines the potential of bifunctional liposomes as high-efficiency and low-toxicity gene delivery system for the treatment of central nervous system disorders.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nursing and Allied Sciences, North Dakota State University, Fargo, North Dakota 58105, USA.
authors.forename: Gitanjali
authors.initials: G
authors.lastname: Sharma
authors.forename: Amit
authors.initials: A
authors.lastname: Modgil
authors.forename: Chengwen
authors.initials: C
authors.lastname: Sun
authors.forename: Jagdish
authors.initials: J
authors.lastname: Singh
mesh_terms: D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism; D002478:Cells, Cultured; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D014162:Transfection; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; D008081:Liposomes; D010455:Peptides; D014168:Transferrin; C015462:polyarginine; D011092:Polyethylene Glycols