title: Targeted brain delivery of itraconazole via RVG29 anchored nanoparticles.
abstract: The blood-brain barrier is a major barrier in the neurological diseases treatment and precludes the entry of drugs from blood to brain. Here, we developed 29-amino-acid peptide derived from rabies virus glycoprotein (RVG29) peptide conjugated itraconazole-loaded albumin nanoparticles (RVG29-ITZ-NPs). The RVG29 peptide was conjugated to the albumin NPs using biotin-binding streptavidin as crosslinker. The NPs were characterized in terms of particle size, zeta potential, drug loading and release behavior in vitro. Cellular uptake of RVG29-ITZ-NPs was investigated by flow cytometry. Pharmacokinetics and brain distribution of RVG29-ITZ-NPs were investigated after intravenous administration of NPs. The particle size of RVG29-ITZ-NPs was 89.3 ± 1.9 nm as determined by dynamic light scattering. The zeta potential of RVG29-ITZ-NPs was -33.1 ± 0.9 mV. RVG29-ITZ-NPs exhibited a sustained release profile within 24 h. In vitro cellular uptake studies demonstrated that RVG29 significantly facilitated the intracellular delivery of NPs. A significant (P < 0.05) accumulation of ITZ in brain was observed for RVG29-ITZ-NPs as compared with ITZ-NPs and cyclodextrin formulation of ITZ (ITZ-CD). These results suggested that RVG29-ITZ-NPs can be exploited as a potential therapeutic formulation for the intracranial fungal infection.
authors.affiliation: Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Changyou
authors.initials: C
authors.lastname: Zhan
authors.forename: Bing
authors.initials: B
authors.lastname: Gu
authors.forename: Qinggang
authors.initials: Q
authors.lastname: Meng
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
authors.forename: Huimin
authors.initials: H
authors.lastname: Hou
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry*; D001710:Biotin / Q000737:chemistry; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001921:Brain; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D042783:Endothelial Cells / Q000187:drug effects*; D005079:Excipients; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010446:Peptide Fragments / Q000737:chemistry*; D051381:Rats; D012709:Serum Albumin / Q000737:chemistry; D013535:Suspensions; D014759:Viral Envelope Proteins / Q000737:chemistry*
chemical_list: D000956:Antigens, Viral; D003505:Cyclodextrins; D004337:Drug Carriers; D005079:Excipients; D006023:Glycoproteins; D010446:Peptide Fragments; D012709:Serum Albumin; D013535:Suspensions; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus; D017964:Itraconazole; D001710:Biotin