title: Brain-targeted delivery of protein using chitosan- and RVG peptide-conjugated, pluronic-based nano-carrier.
abstract: Brain-targeted delivery of drug or imaging agent is hard to achieve efficiently due to the infiltrative nature of the blood-brain barrier (BBB). Moreover, delivery of therapeutic proteins to brain tissue is further limited by the size and physic-chemical properties of proteins. In this work, we developed a chitosan-conjugated Pluronic-based nano-carrier with a specific target peptide for the brain (rabies virus glycoprotein; RVG29) and applied for the protein delivery to the brain. The in-vivo brain accumulation of the nano-carrier in mice followed i.v injection was optically monitored with Cy5.5-conjugation to the nano-carrier, and the result showed that the Pluronic-based nano-carrier conjugated with both chitosan and the peptide was very efficient for the accumulation in brain tissue and was remarkably better than the nano-carrier conjugated with the peptide only. β-galactosidase, a model protein, was also delivered and accumulated efficiently in the brain by loading in the nano-carrier, analyzed by the bio-distribution of β-galactosidase. The delivered protein in the brain also maintained its bioactivity. Therefore, RVG29- and chitosan-conjugated Pluronic-based nano-carrier could be potentially useful for the diagnosis and therapy of brain diseases.
authors.affiliation: School of Materials Science and Engineering and Department of Nanobio Materials and Electronics, Gwangju Institute of Science and Technology, 123 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, Republic of Korea.
authors.forename: Ja-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Won Il
authors.initials: WI
authors.lastname: Choi
authors.forename: Young Ha
authors.initials: YH
authors.lastname: Kim
authors.forename: Giyoong
authors.initials: G
authors.lastname: Tae
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D048271:Chitosan / Q000737:chemistry*; D004058:Diffusion; D006023:Glycoproteins / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D010455:Peptides / Q000493:pharmacokinetics; D020442:Poloxamer / Q000493:pharmacokinetics*; D011820:Rabies virus / Q000737:chemistry*; D014018:Tissue Distribution; D001616:beta-Galactosidase / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D006023:Glycoproteins; D053769:Nanocapsules; D010455:Peptides; D020442:Poloxamer; D048271:Chitosan; D001616:beta-Galactosidase