title: Functionalized nanoscale micelles with brain targeting ability and intercellular microenvironment biosensitivity for anti-intracranial infection applications.
abstract: Due to complication factors such as blood-brain barrier (BBB), integrating high efficiency of brain target ability with specific cargo releasing into one nanocarrier seems more important. A brain targeting nanoscale system is developed using dehydroascorbic acid (DHA) as targeting moiety. DHA has high affinity with GLUT1 on BBB. More importantly, the GLUT1 transportation of DHA represents a "one-way" accumulative priority from blood into brain. The artificial micelles are fabricated by a disulfide linkage, forming a bio-responsive inner barrier, which can maintain micelles highly stable in circulation and shield the leakage of entrapped drug before reaching the targeting cells. The designed micelles can cross BBB and be further internalized by brain cells. Once within the cells, the drug release can be triggered by high intracellular level of glutathione (GSH). Itraconazole (ITZ) is selected as the model drug because of its poor brain permeability and low stability in blood. It demonstrates that the functionalized nanoscale micelles can achieve highly effective direct drug delivery to targeting site. Based on the markedly increased stability in blood circulation and improved brain delivery efficiency of ITZ, DHA-modified micelles show highly effective in anti-intracranial infection. Therefore, this smart nanodevice shows a promising application for the treatment of brain diseases.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Shao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Ding
authors.forename: Shixian
authors.initials: S
authors.lastname: Huang
authors.forename: Jiqin
authors.initials: J
authors.lastname: Wu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.forename: Chunfu
authors.initials: C
authors.lastname: Yang
authors.forename: Qibin
authors.initials: Q
authors.lastname: Leng
authors.forename: Liya
authors.initials: L
authors.lastname: Ye
authors.forename: Jinning
authors.initials: J
authors.lastname: Lou
authors.forename: Liping
authors.initials: L
authors.lastname: Zhu
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D060833:Cellular Microenvironment; D003683:Dehydroascorbic Acid / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005453:Fluorescence; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008823:Micelles; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry*; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D008823:Micelles; D005978:Glutathione; D005947:Glucose; D003683:Dehydroascorbic Acid
keywords: GSH-triggered; brain targeting; dehydroascorbic acid; intracranial infection; polymeric micelles