title: Targeting the brain with PEG-PLGA nanoparticles modified with phage-displayed peptides.
abstract: The relative impermeability of the blood-brain barrier (BBB) results from tight junctions and efflux transport systems limits drug delivery to the central nervous system (CNS), and thus severely restricts the therapy of many central nervous system diseases. In order to enhance the brain-specific drug delivery, we employed a 12-mer phage display peptide library to isolate peptides that could target the drug delivery system to the brain. A 12-amino-acid-peptide (denoted as Pep TGN) which was displayed by bacteriophage Clone 12-2 was finally selected by rounds of in vivo screening. Pep TGN was covalently conjugated onto the surface of poly (ethyleneglycol)-poly (lactic-co-glycolic acid) (PEG-PLGA) based nanoparticles (NPs). The cellular uptake of Pep TGN decorated nanoparticles was significantly higher than that of unmodified nanoparticles when incubated with bEnd.3 cells. Enhanced brain accumulation efficiency together with lower accumulation in liver and spleen was observed in the nude mice intravenously injected with Pep TGN conjugated nanoparticles compared with those injected with plain nanoparticles, showing powerful brain selectivity of Pep TGN. Coumarin 6 was used as a fluorescent probe for the evaluation of brain delivery properties. The brain Drug Targeting Index (DTI) of coumarin 6 incorporated in targeted nanoparticles was significantly higher than that of coumarin 6 incorporated in plain nanoparticles. In conclusion, the Pep TGN is a motif never been reported before and Pep TGN modified nanoparticles showed great potential in targeted drug delivery across the blood brain barrier.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai 201203, People's Republic of China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zha
authors.forename: Liangran
authors.initials: L
authors.lastname: Guo
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Wang
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
authors.forename: Longping
authors.initials: L
authors.lastname: Wen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D019151:Peptide Library; D010455:Peptides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols