Transferrin-Conjugated Magnetic Dextran-Spermine Nanoparticles for Targeted Drug Transport Across Blood-Brain Barrier Publisher Pubmed



Ghadiri M¹ ; Vasheghanifarahani E¹ ; Atyabi F² ; Kobarfard F³ ; Mohamadyartoupkanlou F⁴ ; Hosseinkhani H⁵
Source: Journal of Biomedical Materials Research - Part A Published:2017

Abstract

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. © 2017 Wiley Periodicals, Inc.