Transferrin‐conjugated magnetic dextran‐spermine nanoparticles for targeted drug transport across blood‐brain barrier

• Published in: Journal of biomedical materials research. Part A 2017-10, Vol.105 (10), p.2851-2864
• Main Authors: Ghadiri, Maryam, Vasheghani‐Farahani, Ebrahim, Atyabi, Fatemeh, Kobarfard, Farzad, Mohamadyar‐Toupkanlou, Farzaneh, Hosseinkhani, Hossein
• Format: Article
• Language: English
• Subjects: Animals; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - pharmacokinetics; Biocompatibility; biodistribution; Biopolymers; Blood-brain barrier; Blood-Brain Barrier - metabolism; capecitabine; Capecitabine - administration & dosage; Capecitabine - pharmacokinetics; cationic polymer; Cell Line; Conjugation; Cytotoxicity; Delayed-Action Preparations - chemistry; Dextran; Dextrans - chemistry; Drug delivery; Drug Delivery Systems; Female; Gelation; Humans; Hydrogen-Ion Concentration; In vivo methods and tests; Magnetite Nanoparticles - chemistry; Mice; Nanoparticles; Neuroimaging; pH effects; pH‐sensitive; Spermine; Spermine - chemistry; Staining; targeted delivery; Tissue Distribution; Toxicity; Transferrin; Transferrin - chemistry; Transport; Vibration
• ISSN: 1549-3296; 1552-4965
• DOI: 10.1002/jbm.a.36145

Application of many vital hydrophilic medicines have been restricted by blood–brain barrier (BBB) for treatment of brain diseases. In this study, a targeted drug delivery system based on dextran‐spermine biopolymer was developed for drug transport across BBB. Drug loaded magnetic dextran‐spermine nanoparticles (DS‐NPs) were prepared via ionic gelation followed by transferrin (Tf) conjugation as targeting moiety. The characteristics of Tf conjugated nanoparticles (TDS‐NPs) were analyzed by different methods and their cytotoxicity effects on U87MG cells were tested. The superparamagnetic characteristic of TDS‐NPs was verified by vibration simple magnetometer. Capecitabine loaded TDS‐NPs exhibited pH‐sensitive release behavior with enhanced cytotoxicity against U87MG cells, compared to DS‐NPs and free capecitabine. Prussian‐blue staining and TEM‐imaging showed the significant cellular uptake of TDS‐NPs. Furthermore, a remarkable increase of Fe concentrations in brain was observed following their biodistribution and histological studies in vivo, after 1 and 7 days of post‐injection. Enhanced drug transport across BBB and pH‐triggered cellular uptake of TDS‐NPs indicated that these theranostic nanocarriers are promising candidate for the brain malignance treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2851–2864, 2017.