Functionalized Nanoscale Micelles with Brain Targeting Ability and Intercellular Microenvironment Biosensitivity for Anti-Intracranial Infection Applications

• Published in: Advanced healthcare materials 2015-01, Vol.4 (2), p.291-300
• Main Authors: Shao, Kun, Zhang, Yu, Ding, Ning, Huang, Shixian, Wu, Jiqin, Li, Jianfeng, Yang, Chunfu, Leng, Qibin, Ye, Liya, Lou, Jinning, Zhu, Liping, Jiang, Chen
• Format: Article
• Language: English
• Subjects: Animals; Anti-Infective Agents - pharmacology; Biological Transport - drug effects; Blood-brain barrier; Brain; Brain - cytology; Brain - drug effects; Brain - metabolism; Brain - pathology; brain targeting; Cell Line, Tumor; Cellular Microenvironment; dehydroascorbic acid; Dehydroascorbic Acid - chemistry; Dehydroascorbic Acid - metabolism; Diseases; Drug Delivery Systems; Drugs; Endocytosis - drug effects; Endothelial Cells - cytology; Endothelial Cells - metabolism; Fluorescence; Glucose - metabolism; Glutathione - metabolism; GSH-triggered; Humans; Immunosuppression; Intracellular Space - drug effects; Intracellular Space - metabolism; intracranial infection; Mice; Micelles; Microscopy, Atomic Force; Nanoparticles - chemistry; Nanostructure; Permeability; polymeric micelles; Tissue Distribution - drug effects
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201400214

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. Functional nanoscale micelles with brain permeability and controlled drug deposition in brain are developed. Biosensitive “‐S‐S‐” barriers are fabricated in cores of nanodevices. The brain targeting ability is achieved by the modification of dehydroascorbic acid (DHA), which has high affinity to blood‐brain barrier (BBB). This smart nanodevice provides a valid approach to achieve highly effective brain diseases therapy.